Androgen Receptor Interacts with Telomeric Proteins in Prostate Cancer Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jan 30

PMID 20110352

Citations 21

Authors

Sahn-Ho Kim

Michelle Richardson

Kannagi Chinnakannu

V Uma Bai

Mani Menon

Evelyn R Barrack

G Prem-Veer Reddy

Affiliations

Soon will be listed here.

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 suggest that AR-antagonist Casodex-mediated cell death may be due to telomere complex disruption.

Citing Articles

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Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC.

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