The androgen receptor malignancy shift in prostate cancer

The Prostate
Ben T CopelandJeremy O Jones

Abstract

Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications. In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells. Reinterpretation of ...Continue Reading

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Citations

Aug 14, 2018·Journal of Biochemical and Molecular Toxicology·Isil Ezgi EryilmazBerrin Tunca
Oct 20, 2018·The Journal of Clinical Investigation·Adam SharpStephen R Plymate
Mar 14, 2019·Endocrine-related Cancer·Suzan StellooWilbert Zwart
Sep 15, 2019·Molecular Oncology·Ben T CopelandJeremy O Jones
Nov 28, 2019·Molecular and Cellular Biochemistry·Aymen ShatnawiEfrosini Tsouko
May 8, 2019·Cell Biochemistry and Function·Md Tariqul IslamHanchun Chen
Jun 16, 2019·International Journal of Molecular Sciences·Simon J BaumgartBernard Haendler

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