Skip to main content

CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.

Publication ,  Journal Article
Alfaqih, MA; Nelson, ER; Liu, W; Safi, R; Jasper, JS; Macias, E; Geradts, J; Thompson, JW; Dubois, LG; Freeman, MR; Chang, C-Y; Chi, J-T ...
Published in: 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 homeostasis. Importantly, lower CYP27A1 transcript levels were associated with shorter disease-free survival and higher tumor grade. Loss of CYP27A1 in prostate cancer was confirmed at the protein level by immunostaining for CYP27A1 in annotated tissue microarrays. Restoration of CYP27A1 expression in cells where its gene was silenced attenuated their growth in vitro and in tumor xenografts. Studies performed in vitro revealed that treatment of prostate cancer cells with 27-hydroxycholesterol (27HC), an enzymatic product of CYP27A1, reduced cellular cholesterol content in prostate cancer cell lines by inhibiting the activation of sterol regulatory-element binding protein 2 and downregulating low-density lipoprotein receptor expression. Our findings suggest that CYP27A1 is a critical cellular cholesterol sensor in prostate cells and that dysregulation of the CYP27A1/27HC axis contributes significantly to prostate cancer pathogenesis. Cancer Res; 77(7); 1662-73. ©2017 AACR.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 1, 2017

Volume

77

Issue

7

Start / End Page

1662 / 1673

Location

United States

Related Subject Headings

  • Sterol Regulatory Element Binding Protein 2
  • Receptors, LDL
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Hydroxycholesterols
  • Humans
  • Homeostasis
  • Gene Expression Regulation, Enzymologic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Alfaqih, M. A., Nelson, E. R., Liu, W., Safi, R., Jasper, J. S., Macias, E., … Freedland, S. J. (2017). CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer. Cancer Res, 77(7), 1662–1673. https://doi.org/10.1158/0008-5472.CAN-16-2738
Alfaqih, Mahmoud A., Erik R. Nelson, Wen Liu, Rachid Safi, Jeffery S. Jasper, Everardo Macias, Joseph Geradts, et al. “CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.Cancer Res 77, no. 7 (April 1, 2017): 1662–73. https://doi.org/10.1158/0008-5472.CAN-16-2738.
Alfaqih MA, Nelson ER, Liu W, Safi R, Jasper JS, Macias E, et al. CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer. Cancer Res. 2017 Apr 1;77(7):1662–73.
Alfaqih, Mahmoud A., et al. “CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.Cancer Res, vol. 77, no. 7, Apr. 2017, pp. 1662–73. Pubmed, doi:10.1158/0008-5472.CAN-16-2738.
Alfaqih MA, Nelson ER, Liu W, Safi R, Jasper JS, Macias E, Geradts J, Thompson JW, Dubois LG, Freeman MR, Chang C-Y, Chi J-T, McDonnell DP, Freedland SJ. CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer. Cancer Res. 2017 Apr 1;77(7):1662–1673.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 1, 2017

Volume

77

Issue

7

Start / End Page

1662 / 1673

Location

United States

Related Subject Headings

  • Sterol Regulatory Element Binding Protein 2
  • Receptors, LDL
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Hydroxycholesterols
  • Humans
  • Homeostasis
  • Gene Expression Regulation, Enzymologic