Androgen receptor interacts with telomeric proteins in prostate cancer cells.

The Journal of Biological Chemistry
Sahn-Ho KimG Prem-Veer Reddy

Abstract

The telomeric complex, shelterin, plays a critical role in protecting chromosome ends from erosion, and disruption of these complexes can lead to chromosomal instability culminating in cell death or malignant transformation. We reported previously that dominant-negative mutants of one of the telomeric proteins called TIN2 cause death of androgen receptor (AR)-negative but not AR-positive prostate cancer cells, raising the question of a possible role of AR in the structural stability of telomeric complexes. Consistent with this possibility, in the present study, we observed that the AR antagonist Casodex (bicalutamide) disrupted telomeric complexes in AR-positive LNCaP cells but not in AR-negative PC-3 cells. Immunofluorescent studies revealed colocalization of TIN2 and AR. Reciprocal immunoprecipitation studies showed association of AR with telomeric proteins. Furthermore, telomeric proteins were overexpressed in prostate cancer cells compared with normal prostate epithelial cells, and sucrose density gradient analysis showed co-sedimentation of AR with telomeric proteins in a shelterin-like mega complex. Together, these observations suggest an allosteric role of AR in telomere complex stability in prostate cancer cells and sug...Continue Reading

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Citations

Dec 11, 1992·Biochimica Et Biophysica Acta·D Hoekstra, J W Kok
May 9, 2012·Asian Journal of Andrology·Sahn-Ho KimG Prem Veer Reddy
Mar 1, 2013·Endocrine-related Cancer·Natalie SampsonIris E Eder
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Jul 5, 2017·Nature Reviews. Urology·Mindy Kim Graham, Alan Meeker
Sep 4, 2015·The Journal of Biological Chemistry·Vidyavathi ReddySahn-Ho Kim
Feb 19, 2021·Cellular and Molecular Life Sciences : CMLS·Semih Can AkincilarVinay Tergaonkar
Sep 7, 2021·Journal of the Egyptian National Cancer Institute·Gabriel Arantes Dos SantosMiguel Srougi

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