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BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.


ABSTRACT:

Background

We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR.

Methods

Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively.

Results

BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome.

Conclusions

In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.

SUBMITTER: Kuo PC 

PROVIDER: S-EPMC4453457 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.

Kuo P-C PC   Huang C-W CW   Lee C-I CI   Chang H-W HW   Hsieh S-W SW   Chung Y-P YP   Lee M-S MS   Huang C-S CS   Tsao L-P LP   Tsao Y-P YP   Chen S-L SL  

British journal of cancer 20141202 2


<h4>Background</h4>We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR.<h4>Methods</h4>Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistoc  ...[more]

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