BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability
Journal
British Journal of Cancer
Journal Volume
112
Journal Issue
2
Pages
391-402
Date Issued
2015
Author(s)
Kuo P.-C.
Huang C.-W.
Lee C.-I.
Chang H.-W.
Hsieh S.-W.
Chung Y.-P.
Tsao L.-P.
Tsao Y.-P.
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. ? 2015 Cancer Research UK. All rights reserved.
SDGs
Other Subjects
androgen receptor; breast carcinoma amplified sequence 2; heat shock protein 90; messenger RNA; protein p53; regulator protein; tanespimycin; unclassified drug; androgen receptor; BCAS2 protein, human; benzoquinone derivative; heat shock protein 90; macrocyclic lactam; proteasome; protein p53; TP53 protein, human; tumor protein; Article; carboxy terminal sequence; cell growth; cell proliferation; controlled study; correlation analysis; cytosol; DNA binding; fluorescence microscopy; genetic transcription; Gleason score; growth rate; half life time; hinge region; human; human cell; IC50; immunohistochemistry; immunoprecipitation; in vitro study; LNCaP cell line; male; MTT assay; priority journal; promoter region; prostate cancer; protein degradation; protein expression; protein protein interaction; protein stability; real time polymerase chain reaction; receptor upregulation; RNA splicing; transient transfection; Western blotting; antagonists and inhibitors; cancer grading; cell proliferation; gene expression regulation; genetics; HEK293 cell line; metabolism; pathology; physiology; prostate tumor; protein stability; tumor cell line; Benzoquinones; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Half-Life; HEK293 Cells; HSP90 Heat-Shock Proteins; Humans; Inhibitory Concentration 50; Lactams, Macrocyclic; Male; Neoplasm Grading; Neoplasm Proteins; Prostatic Neoplasms; Proteasome Endopeptidase Complex; Protein Stability; Proteolysis; Receptors, Androgen; Transcription, Genetic; Tumor Suppressor Protein p53
Publisher
Nature Publishing Group
Type
journal article