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Ching-yi Chang

Associate Research Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology
Box 103057, Durham, NC 27710
Medical Science Res Bldg III, 3 Genome Court, Durham, NC 27710

Selected Publications


Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Journal Article Cancer Res · September 1, 2023 UNLABELLED: Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term surviv ... Full text Link to item Cite

Data from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <div>Abstract<p>Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains hi ... Full text Cite

Supplementary Figures 1-4 and Tables 1-2 from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <p>Contains Supplementary Figures 1-4, Supplementary Tables 1-2 and legends for Supplementary Videos 1-4</p> ... Full text Cite

Supplementary Figures 1-4 and Tables 1-2 from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <p>Contains Supplementary Figures 1-4, Supplementary Tables 1-2 and legends for Supplementary Videos 1-4</p> ... Full text Cite

Data from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <div>Abstract<p>Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains hi ... Full text Cite

Data from Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells

Other · April 4, 2023 <div>Abstract<p>Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression ... Full text Cite

Data from Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells

Other · April 4, 2023 <div>Abstract<p>Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression ... Full text Cite

Estrogen Receptor Signaling in the Immune System.

Journal Article Endocr Rev · January 12, 2023 The immune system functions in a sexually dimorphic manner, with females exhibiting more robust immune responses than males. However, how female sex hormones affect immune function in normal homeostasis and in autoimmunity is poorly understood. In this rev ... Full text Link to item Cite

Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells.

Journal Article Cancer Immunol Res · January 3, 2023 Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells fac ... Full text Link to item Cite

Eosinophilia in cancer and its regulation by sex hormones.

Journal Article Trends Endocrinol Metab · January 2023 Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrog ... Full text Link to item Cite

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Journal Article Cancer Res · September 1, 2023 UNLABELLED: Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term surviv ... Full text Link to item Cite

Data from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <div>Abstract<p>Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains hi ... Full text Cite

Supplementary Figures 1-4 and Tables 1-2 from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <p>Contains Supplementary Figures 1-4, Supplementary Tables 1-2 and legends for Supplementary Videos 1-4</p> ... Full text Cite

Supplementary Figures 1-4 and Tables 1-2 from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <p>Contains Supplementary Figures 1-4, Supplementary Tables 1-2 and legends for Supplementary Videos 1-4</p> ... Full text Cite

Data from Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis

Other · September 1, 2023 <div>Abstract<p>Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains hi ... Full text Cite

Data from Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells

Other · April 4, 2023 <div>Abstract<p>Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression ... Full text Cite

Data from Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells

Other · April 4, 2023 <div>Abstract<p>Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression ... Full text Cite

Estrogen Receptor Signaling in the Immune System.

Journal Article Endocr Rev · January 12, 2023 The immune system functions in a sexually dimorphic manner, with females exhibiting more robust immune responses than males. However, how female sex hormones affect immune function in normal homeostasis and in autoimmunity is poorly understood. In this rev ... Full text Link to item Cite

Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells.

Journal Article Cancer Immunol Res · January 3, 2023 Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells fac ... Full text Link to item Cite

Eosinophilia in cancer and its regulation by sex hormones.

Journal Article Trends Endocrinol Metab · January 2023 Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrog ... Full text Link to item Cite

Development and Characterization of a Luciferase Labeled, Syngeneic Murine Model of Ovarian Cancer.

Journal Article Cancers (Basel) · August 30, 2022 Despite advances in surgery and targeted therapies, the prognosis for women with high-grade serous ovarian cancer remains poor. Moreover, unlike other cancers, immunotherapy has minimally impacted outcomes in patients with ovarian cancer. Progress in this ... Full text Open Access Link to item Cite

Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma.

Journal Article J Clin Invest · December 1, 2021 Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater be ... Full text Open Access Link to item Cite

Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer.

Journal Article Nat Commun · August 24, 2021 Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure ... Full text Link to item Cite

The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor.

Journal Article Mol Cancer Ther · July 2020 The estrogen receptor (ER/ESR1) is expressed in a majority of breast cancers and drugs that inhibit ER signaling are the cornerstone of breast cancer pharmacotherapy. Currently, aromatase inhibitors are the frontline endocrine interventions of choice altho ... Full text Link to item Cite

The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.

Journal Article Cell Rep · October 22, 2019 Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistance is nearly in ... Full text Link to item Cite

Constitutively active ESR1 mutations in gynecologic malignancies and clinical response to estrogen-receptor directed therapies.

Journal Article Gynecol Oncol · July 2019 OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially ... Full text Link to item Cite

Inhibition of ERRα Prevents Mitochondrial Pyruvate Uptake Exposing NADPH-Generating Pathways as Targetable Vulnerabilities in Breast Cancer.

Journal Article Cell Rep · June 18, 2019 Most cancer cells exhibit metabolic flexibility, enabling them to withstand fluctuations in intratumoral concentrations of glucose (and other nutrients) and changes in oxygen availability. While these adaptive responses make it difficult to achieve clinica ... Full text Link to item Cite

CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer.

Journal Article Nat Commun · June 4, 2019 Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myelo ... Full text Link to item Cite

Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function.

Journal Article Sci Signal · June 26, 2018 Thyroid hormone receptor β1 (THRB1) and estrogen-related receptor α (ESRRA; also known as ERRα) both play important roles in mitochondrial activity. To understand their potential interactions, we performed transcriptome and ChIP-seq analyses and found that ... Full text Link to item Cite

Validation of histone deacetylase 3 as a therapeutic target in castration-resistant prostate cancer.

Journal Article Prostate · March 2018 BACKGROUND: Whereas the androgen receptor (AR) signaling axis remains a therapeutic target in castration-resistant prostate cancer (CRPC), the emergence of AR mutations and splice variants as mechanisms underlying resistance to contemporary inhibitors of t ... Full text Link to item Cite

Neomorphic ERα Mutations Drive Progression in Breast Cancer and Present a Challenge for New Drug Discovery.

Journal Article Cancer Cell · February 12, 2018 In this issue of Cancer Cell, Jeselsohn et al. dissect the function of several of the most clinically important estrogen receptor alpha mutants associated with endocrine therapy resistance in breast cancer and demonstrate that they manifest disease-relevan ... Full text Open Access Link to item Cite

The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.

Journal Article Nature communications · October 2017 Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here ... Full text Cite

Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer.

Journal Article Endocr Relat Cancer · July 2017 The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, whic ... Full text Link to item Cite

CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.

Journal Article Cancer Res · April 1, 2017 In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol ... Full text Link to item Cite

ERRα-Regulated Lactate Metabolism Contributes to Resistance to Targeted Therapies in Breast Cancer.

Journal Article Cell Rep · April 12, 2016 Imaging studies in animals and in humans have indicated that the oxygenation and nutritional status of solid tumors is dynamic. Furthermore, the extremely low level of glucose within tumors, while reflecting its rapid uptake and metabolism, also suggests t ... Full text Link to item Cite

The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer.

Journal Article Climacteric · December 2014 Despite increased survivorship among patients, breast cancer remains the most common cancer among women and is the second leading cause of cancer death in women. The magnitude of this problem provides a strong impetus for new chemopreventative strategies a ... Full text Link to item Cite

Cholesterol and breast cancer pathophysiology.

Journal Article Trends Endocrinol Metab · December 2014 Cholesterol is a risk factor for breast cancer although the mechanisms by which this occurs are not well understood. One hypothesis is that dyslipidemia results in increased cholesterol content in cell membranes, thus impacting upon membrane fluidity and s ... Full text Link to item Cite

Abstract 3311: The cholesterol/ 27-hydroxycholesterol axis is a novel therapeutic target in castrate resistant prostate cancer

Conference Cancer Research · October 1, 2014 AbstractThe most recent estimates indicate that men have a seventeen percent chance of developing invasive prostate cancer (PCa) over their lifetime. This makes PCa the most commonly diagnosed malignancy amo ... Full text Cite

Abstract 4570: Role of ERRalpha in ovarian cancer

Conference Cancer Research · October 1, 2014 AbstractObjective. The estrogen receptor-related receptor-alpha (ERRα, encoded by ESRRA) has emerged as a key transcriptional regulator of mitochondrial function and has been implicated as a prognostic marke ... Full text Cite

Obesity, cholesterol metabolism, and breast cancer pathogenesis.

Journal Article Cancer Res · September 15, 2014 Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the i ... Full text Link to item Cite

4,4'-Unsymmetrically substituted 3,3'-biphenyl alpha helical proteomimetics as potential coactivator binding inhibitors.

Journal Article Bioorg Med Chem · January 15, 2014 A series of unsymmetrically substituted biphenyl compounds was designed as alpha helical proteomimetics with the aim of inhibiting the binding of coactivator proteins to the nuclear hormone receptor coactivator binding domain. These compounds were synthesi ... Full text Link to item Cite

Molecular pathways: the metabolic regulator estrogen-related receptor α as a therapeutic target in cancer.

Journal Article Clin Cancer Res · November 15, 2012 The estrogen-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily of transcription factors whose activity is regulated by the expression level and/or activity of its obligate coregulators, peroxisome proliferator-activated rece ... Full text Link to item Cite

3,3'-Disubstituted bipolar biphenyls as inhibitors of nuclear receptor coactivator binding.

Journal Article Bioorg Med Chem Lett · November 1, 2012 A series of bipolar biphenyl compounds was synthesized as proteomimetic analogs of the LXXLL penta-peptide motif responsible for the binding of coactivator proteins to the nuclear hormone receptor coactivator binding domain. These compounds were subjected ... Full text Link to item Cite

Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation.

Journal Article Proc Natl Acad Sci U S A · November 8, 2011 Stimulation of resting CD4(+) T lymphocytes leads to rapid proliferation and differentiation into effector (Teff) or inducible regulatory (Treg) subsets with specific functions to promote or suppress immunity. Importantly, Teff and Treg use distinct metabo ... Full text Link to item Cite

The metabolic regulator ERRα, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.

Journal Article Cancer Cell · October 18, 2011 A genomic signature designed to assess the activity of the estrogen-related receptor alpha (ERRα) was used to profile more than 800 breast tumors, revealing a shorter disease-free survival in patients with tumors exhibiting elevated receptor activity. Impo ... Full text Link to item Cite

Identification of ligand-selective peptide antagonists of the mineralocorticoid receptor using phage display.

Journal Article Mol Endocrinol · January 2011 The mineralocorticoid receptor (MR) is a member of the nuclear receptor superfamily. Pathological activation of the MR causes cardiac fibrosis and heart failure, but clinical use of MR antagonists is limited by the renal side effect of hyperkalemia. The gl ... Full text Link to item Cite

Mechanisms of progesterone receptor inhibition of inflammatory responses in cellular models of breast cancer.

Journal Article Mol Endocrinol · December 2010 Both pro- and antimitogenic activities have been ascribed to progesterone receptor (PR) agonists and antagonists in breast cancer cells; however, the transcriptional responses that underlie these paradoxical functions are not apparent. Using nontransformed ... Full text Link to item Cite

WNT11 expression is induced by estrogen-related receptor alpha and beta-catenin and acts in an autocrine manner to increase cancer cell migration.

Journal Article Cancer Res · November 15, 2010 Elevated expression of the orphan nuclear receptor estrogen-related receptor α (ERRα) has been associated with a negative outcome in several cancers, although the mechanism(s) by which this receptor influences the pathophysiology of this disease and how it ... Full text Link to item Cite

ERRgamma regulates cardiac, gastric, and renal potassium homeostasis.

Journal Article Mol Endocrinol · February 2010 Energy production by oxidative metabolism in kidney, stomach, and heart, is primarily expended in establishing ion gradients to drive renal electrolyte homeostasis, gastric acid secretion, and cardiac muscle contraction, respectively. In addition to orches ... Full text Link to item Cite

The homeodomain protein HOXB13 regulates the cellular response to androgens.

Journal Article Mol Cell · November 13, 2009 HOXB13 is a member of the homeodomain family of sequence-specific transcription factors and, together with the androgen receptor (AR), plays a critical role in the normal development of the prostate gland. We demonstrate here that, in prostate cancer cells ... Full text Link to item Cite

Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.

Journal Article Mol Endocrinol · August 2009 The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic stat ... Full text Link to item Cite

Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands.

Journal Article Chem Biol · April 24, 2009 The pharmacological activity of different nuclear receptor ligands is reflected by their impact on receptor structure. Thus, we asked whether differential presentation of protein-protein interaction surfaces on the androgen receptor (AR), a surrogate assay ... Full text Link to item Cite

Purification and characterization of recombinant human mineralocorticoid receptor.

Journal Article Mol Cell Endocrinol · April 10, 2009 The mineralocorticoid receptor (MR) plays a critical role in the maintenance of electrolyte homeostasis and blood pressure via direct effects on the distal nephron and the cardiovascular system. The MR also has an important role in the pathology of cardiov ... Full text Link to item Cite

Estrogen-related receptor alpha is critical for the growth of estrogen receptor-negative breast cancer.

Journal Article Cancer Res · November 1, 2008 Expression of estrogen-related receptor alpha (ERRalpha) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of this orphan nuclear receptor in tumor growth and progression, however, is yet to ... Full text Link to item Cite

The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs.

Journal Article Arch Biochem Biophys · April 15, 2007 The vitamin D receptor (VDR) mediates the biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) through its capacity to recruit coregulatory proteins. This interaction is mediated via a coregulatory LxxLL motif. We screened a combinatorial (x)7LxxLL ... Full text Link to item Cite

Ligand-specific dynamics of the androgen receptor at its response element in living cells.

Journal Article Mol Cell Biol · March 2007 Androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. Androgens act through the androgen receptor (AR), which is a ligand-modulated transcription factor. Antiandrogen ... Full text Link to item Cite

Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.

Journal Article Mol Cell · December 8, 2006 In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor ... Full text Link to item Cite

Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators.

Journal Article Mol Endocrinol · June 2006 We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to es ... Full text Link to item Cite

Development of peptide antagonists for the androgen receptor using combinatorial peptide phage display.

Journal Article Mol Endocrinol · October 2005 Under the auspices of the Nuclear Receptor Signaling Atlas (NURSA), we have undertaken to evaluate the feasibility of targeting nuclear receptor-coactivator surfaces for new drug discovery. The underlying objective of this approach is to provide the resear ... Full text Link to item Cite

Androgen receptor-cofactor interactions as targets for new drug discovery.

Journal Article Trends Pharmacol Sci · May 2005 Cofactor recruitment is a crucial regulatory step in nuclear receptor signal transduction. Given the obligate nature of interactions between cofactors and these receptors for transcriptional activity, it is likely that drugs that target coactivator interac ... Full text Link to item Cite

Single-step purification of full-length human androgen receptor.

Journal Article Nuclear receptor signaling · January 2005 The full-length human androgen receptor with an N-terminal biotin acceptor peptide tag was overexpressed in Spodoptera frugiperda cells in the presence of 1 microM dihydrotestosterone. Site-specific biotinylation of BAP was achieved in vivo by co-expressio ... Full text Cite

Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor RORgamma.

Journal Article Biochem Biophys Res Commun · March 19, 2004 The retinoid-related orphan receptor gamma (RORgamma) has been shown to function as a positive regulator of transcription in many cell lines. Transcriptional activation by nuclear receptors involves recruitment of co-activators that interact with receptors ... Full text Link to item Cite

Pharmacological uncoupling of androgen receptor-mediated prostate cancer cell proliferation and prostate-specific antigen secretion.

Journal Article Cancer Res · November 15, 2003 The androgen receptor (AR), a member of the nuclear receptor family, is a ligand-inducible transcription factor. In the prostate gland, androgens regulate the transcription of several genes that ultimately result in cell growth and differentiation. With a ... Link to item Cite

Synthetic LXXLL peptide antagonize 1,25-dihydroxyvitamin D3-dependent transcription.

Journal Article J Cell Biochem · February 1, 2003 The vitamin D receptor (VDR) is known to mediate the biological actions of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) through its ability to regulate cellular programs of gene expression. We identified VDR- and retinoid X receptor (RXR)-interacting LXXLL ... Full text Link to item Cite

Role of the aryl hydrocarbon receptor in cell cycle regulation.

Journal Article Toxicology · December 27, 2002 One of the most puzzling aspects of the biological impact of polycyclic aromatic hydrocarbon compounds is that they elicit an apparently unrelated variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. At the cellular l ... Full text Link to item Cite

Inhibition of 1,25-dihydroxyvitamin D3-dependent transcription by synthetic LXXLL peptide antagonists that target the activation domains of the vitamin D and retinoid X receptors.

Journal Article J Bone Miner Res · December 2002 The vitamin D receptor (VDR) is known to mediate the biological actions of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] through its ability to regulate cellular programs of gene expression. Although RXR appears to participate as a heterodimeric partner with the ... Full text Link to item Cite

Elucidation of the molecular mechanism of action of selective estrogen receptor modulators.

Journal Article Am J Cardiol · July 3, 2002 The term selective estrogen receptor modulator (SERM) describes a group of pharmaceuticals that manifest estrogen receptor (ER) agonist activity in some tissues but opposes estrogen action in others. Although the name describing this class of drugs is new, ... Full text Link to item Cite

Evaluation of ligand-dependent changes in AR structure using peptide probes.

Journal Article Mol Endocrinol · April 2002 Featured Publication Mutations in the AR are frequently found in relapsed prostate cancers, some of which permit antiandrogens as well as nonandrogenic compounds to function as androgens. However, the molecular mechanism(s) by which these mutations enable this aberrant AR phar ... Full text Link to item Cite

Ligand-selective interactions of ER detected in living cells by fluorescence resonance energy transfer.

Journal Article Mol Endocrinol · March 2002 Some aspects of ligand-regulated transcription activation by the estrogen receptor (ER) are associated with the estrogen-dependent formation of a hydrophobic cleft on the receptor surface. At least in vitro, this cleft is required for direct interaction of ... Full text Link to item Cite

Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators.

Journal Article Recent Prog Horm Res · 2002 The term selective estrogen receptor modulators describes a group of pharmaceuticals that function as estrogen receptor (ER) agonists in some tissues but that oppose estrogen action in others. Although the name for this class of drugs has been adopted only ... Full text Link to item Cite

Glucocorticoids manifest androgenic activity in a cell line derived from a metastatic prostate cancer.

Journal Article Cancer Res · December 15, 2001 Featured Publication The pathophysiological mechanism(s) by which androgen independence develops in prostate cancer remains to be determined. The identification in many prostate cancer specimens of a mutant androgen receptor, T877A, with altered ligand specificity has provided ... Link to item Cite

Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM.

Journal Article Ann N Y Acad Sci · December 2001 The term Selective Estrogen Receptor Modulators (SERMs) has been used of late to describe a group of pharmaceuticals that manifest estrogen receptor (ER) agonist activity in some tissues, but that oppose estrogen action in others. Whereas the name describi ... Full text Link to item Cite

Development of peptide antagonists that target estrogen receptor beta-coactivator interactions.

Journal Article Mol Endocrinol · December 2000 Featured Publication The biological actions of estrogen are manifest through two genetically distinct estrogen receptors (ER alpha and ER beta) that display nonidentical expression patterns in target tissues. The phenotypic alterations in response to estrogens in mice disrupte ... Full text Link to item Cite

Temporally distinct and ligand-specific recruitment of nuclear receptor-interacting peptides and cofactors to subnuclear domains containing the estrogen receptor.

Journal Article Mol Endocrinol · December 2000 Ligand binding to estrogen receptor (ER) is presumed to regulate the type and timing of ER interactions with different cofactors. Using fluorescence microscopy in living cells, we characterized the recruitment of five different green fluorescent protein (G ... Full text Link to item Cite

Development of peptide antagonists that target estrogen receptor-cofactor interactions.

Journal Article J Steroid Biochem Mol Biol · November 30, 2000 We have developed a series of high-affinity peptide antagonists that inhibit the transcriptional activity of both subtypes of the human estrogen receptor (ERalpha and ERbeta). We believe that it will be possible to develop these peptides, or corresponding ... Full text Link to item Cite

Activation of transcription factors activator protein-1 and nuclear factor-kappaB by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Journal Article Biochem Pharmacol · April 15, 2000 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin), the prototype agonist of the aromatic hydrocarbon (Ah) receptor, is a potent tumor promoter as well as a complete liver carcinogen that produces an oxidative stress response in rodents and in cultured cel ... Full text Link to item Cite

Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest.

Journal Article J Biol Chem · January 28, 2000 Polyhalogenated aromatic hydrocarbons, of which 2,3,7, 8-tetrachloro-p-dioxin (TCDD) is the prototype compound, elicit a variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. In cultured cells, TCDD shows marked effect ... Full text Link to item Cite

Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta.

Journal Article Mol Cell Biol · December 1999 Featured Publication Recruitment of transcriptional coactivators following ligand activation is a critical step in nuclear receptor-mediated target gene expression. Upon binding an agonist, the receptor undergoes a conformational change which facilitates the formation of a spe ... Full text Link to item Cite

Inhibition of CYP1A1 enzyme activity in mouse hepatoma cell culture by soybean isoflavones.

Journal Article Chem Biol Interact · November 15, 1999 The mechanisms by which soybean- and soybean isoflavone-enriched diets inhibit carcinogenesis are not known. We found that the isoflavones genistin and daidzin, and their respective aglucone forms daidzein and genistein, block 2,3,7,8-tetrachlorodibenzo-p- ... Full text Link to item Cite

Peptide antagonists of the human estrogen receptor.

Journal Article Science · July 30, 1999 Featured Publication Estrogen receptor alpha transcriptional activity is regulated by distinct conformational states that are the result of ligand binding. Phage display was used to identify peptides that interact specifically with either estradiol- or tamoxifen-activated estr ... Full text Link to item Cite

Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta.

Journal Article Proc Natl Acad Sci U S A · March 30, 1999 Featured Publication Estrogen receptor (ER) modulators produce distinct tissue-specific biological effects, but within the confines of the established models of ER action it is difficult to understand why. Previous studies have suggested that there might be a relationship betw ... Full text Link to item Cite

Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.

Journal Article Environ Health Perspect · July 1998 Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice t ... Full text Link to item Cite

Constitutive activation of the aromatic hydrocarbon receptor.

Journal Article Mol Cell Biol · January 1998 The ligand-activated aromatic hydrocarbon receptor (AHR) dimerizes with the AHR nuclear translocator (ARNT) to form a functional complex that transactivates expression of the cytochrome P-450 CYP1A1 gene and other genes in the dioxin-inducible [Ah] gene ba ... Full text Link to item Cite

Dioxin induces transcription of fos and jun genes by Ah receptor-dependent and -independent pathways.

Journal Article Toxicol Appl Pharmacol · November 1996 Halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), and polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are environmental contaminants that cause many apparently unrelated toxic effects. In a previous st ... Full text Link to item Cite

Interaction between the Ah receptor and proteins binding to the AP-1-like electrophile response element (EpRE) during murine phase II [Ah] battery gene expression.

Journal Article Biochem Pharmacol · December 22, 1995 We have studied three Phase II genes in the mouse dioxin-inducible [Ah] battery: Nmo1 [encoding NAD(P)H:menadione oxidoreductase], Ahd4 (encoding the cytosolic aldehyde dehydrogenase ALDH3c), and Ugt1*06 (a UDP glucuronosyltransferase). Oxidant-induced Nmo ... Full text Link to item Cite

Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT).

Journal Article Biochem Pharmacol · November 1, 1994 The aromatic hydrocarbon (Ah) receptor complex is a ligand-activated transcriptional activator consisting of at least two protein components. The ligand-binding component is the AhR protein, a cytosolic receptor encoded by the Ahr gene, which, upon ligand ... Full text Link to item Cite

Ten nucleotide differences, five of which cause amino acid changes, are associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 mice.

Journal Article Pharmacogenetics · December 1993 We have analysed by heteroduplex formation (HF), single stranded conformational polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), and nucleotide sequencing the cDNAs of the Ahrb-1 and Ahrd allelic forms of the aromatic hydrocarbon recept ... Full text Link to item Cite