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Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300.

Publication ,  Journal Article
Dietze, EC; Caldwell, LE; Marcom, K; Collins, SJ; Yee, L; Swisshelm, K; Hobbs, KB; Bean, GR; Seewaldt, VL
Published in: Microsc Res Tech
October 1, 2002

Retinoids and retinoic acid receptors (RARs) are important mediators of normal epithelial cell homeostasis. To assess the role of retinoids and RARs in regulating growth arrest and apoptosis in benign and malignant mammary epithelial cells, two model systems were developed: 1) RAR function was suppressed in retinoid-sensitive normal human mammary epithelial cells (HMECs) by the dominant-negative retinoic acid receptor, RARalpha403 (DNRAR), and 2) retinoid-resistant MCF-7 breast cancer cells were transduced with a functional RARbeta2. Inhibition of RAR function by the DNRAR in HMECs resulted in retinoid-resistance, increased proliferation, and dysregulated growth when cells were cultured in reconstituted extracellular matrix (rECM). Expression of RARbeta2 in MCF-7 cells resulted in sensitivity to retinoid-induced growth arrest and apoptosis. The CREB-binding protein (CBP) and the homologous protein p300 are tightly regulated, rate-limiting integrators of diverse signaling pathways and are recruited during retinoid-mediated transcriptional activation. The relationship between retinoid receptor expression, growth regulation, and transcriptional regulation of CBP/p300 is poorly understood. Inhibition of RAR function in HMECs by DNRAR suppressed expression of CBP/p300 and expression of RARbeta2 in MCF-7 cells promoted induction of CBP/p300 when cells were treated with 1.0 microM all-trans-retinoic acid (ATRA). These results suggest that ATRA and RARs regulate growth arrest of HMECs and modulate CBP/p300 protein expression. Since CBP and p300 are normally present in limiting amounts, their regulation by ATRA and RARs may be an important element in the control of transcriptional activation of genes regulating growth arrest and apoptosis.

Duke Scholars

Published In

Microsc Res Tech

DOI

ISSN

1059-910X

Publication Date

October 1, 2002

Volume

59

Issue

1

Start / End Page

23 / 40

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Trans-Activators
  • Retinoids
  • Receptors, Retinoic Acid
  • Nuclear Proteins
  • Microscopy
  • Humans
  • Gene Expression Regulation
  • Female
  • Epithelial Cells
 

Citation

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Dietze, E. C., Caldwell, L. E., Marcom, K., Collins, S. J., Yee, L., Swisshelm, K., … Seewaldt, V. L. (2002). Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300. Microsc Res Tech, 59(1), 23–40. https://doi.org/10.1002/jemt.10174
Dietze, Eric C., L Elizabeth Caldwell, Kelly Marcom, Steven J. Collins, Lisa Yee, Karen Swisshelm, Katherine B. Hobbs, Gregory R. Bean, and Victoria L. Seewaldt. “Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300.Microsc Res Tech 59, no. 1 (October 1, 2002): 23–40. https://doi.org/10.1002/jemt.10174.
Dietze EC, Caldwell LE, Marcom K, Collins SJ, Yee L, Swisshelm K, et al. Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300. Microsc Res Tech. 2002 Oct 1;59(1):23–40.
Dietze, Eric C., et al. “Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300.Microsc Res Tech, vol. 59, no. 1, Oct. 2002, pp. 23–40. Pubmed, doi:10.1002/jemt.10174.
Dietze EC, Caldwell LE, Marcom K, Collins SJ, Yee L, Swisshelm K, Hobbs KB, Bean GR, Seewaldt VL. Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300. Microsc Res Tech. 2002 Oct 1;59(1):23–40.
Journal cover image

Published In

Microsc Res Tech

DOI

ISSN

1059-910X

Publication Date

October 1, 2002

Volume

59

Issue

1

Start / End Page

23 / 40

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Trans-Activators
  • Retinoids
  • Receptors, Retinoic Acid
  • Nuclear Proteins
  • Microscopy
  • Humans
  • Gene Expression Regulation
  • Female
  • Epithelial Cells