ABSTRACT The oncogene _Bcl-2_ is upregulated frequently in prostate tumors following androgen ablation therapy, and Bcl-2 overexpression may contribute to the androgen-refractory relapse of

the disease. However, the molecular mechanism underlying androgenic regulation of Bcl-2 in prostate cancer cells is understood poorly. In this study, we demonstrated that no androgen

response element (ARE) was identified in the androgen-regulated region of the P1 promoter of _Bcl-2_ gene, whereas, we provided evidence that the androgenic effect is mediated by E2F1

protein through a putative E2F-binding site in the promoter. We further demonstrated that retinoblastoma (RB) protein plays a critical role in androgen regulation of Bcl-2. The

abolished completely by specific inhibition of RB function with a mutated E1A. Finally, androgen treatment of LNCaP cells upregulated specifically levels of the cyclin-dependent kinase

inhibitors (CDKIs) p15INK4B and p27KIP1. Ectopic expression of p15INK4B and/or p27KIP1 inhibited Bcl-2 expression. Knockdown of endogenous p15INK4B or p27KIP1 protein with a pool of siRNAs

diminished androgen-induced downregulation of Bcl-2 expression. Therefore, our data indicate that androgens suppress Bcl-2 expression through negatively modulating activities of the E2F site

in the Bcl-2 promoter by activating the CDKI-RB axis. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NUCLEAR ΒARRESTIN1 REGULATES ANDROGEN RECEPTOR FUNCTION IN CASTRATION RESISTANT

PROSTATE CANCER Article 10 March 2021 ESS2 CONTROLS PROSTATE CANCER PROGRESSION THROUGH RECRUITMENT OF CHROMODOMAIN HELICASE DNA BINDING PROTEIN 1 Article Open access 31 July 2023 E2F

TRANSCRIPTION FACTOR 2-ACTIVATED DLEU2 CONTRIBUTES TO PROSTATE TUMORIGENESIS BY UPREGULATING SERUM AND GLUCOCORTICOID-INDUCED PROTEIN KINASE 1 Article Open access 24 January 2022

ABBREVIATIONS * AR: androgen receptor * ARE: androgen response element * RB: retinoblastoma protein * CDK: cyclin-dependent kinase * CDKI: cyclin-dependent kinase inhibitor * ChIP: chromatin

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. (2002). _Cancer Res._, 62, 1008–1013. Download references ACKNOWLEDGEMENTS We thank Drs LM Boxer, RJ Kelm, JR Nevins, and Z Zacksenhaus for plasmids. This work was supported in part by a

grant (DK60920) from the National Institutes of Health and a grant from the TJ Martell Foundation (DJT), and a developmental award of the Mayo Prostate Cancer SPORE (CA91956) funded by the

National Cancer Institute (HH). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Departments of Urology and Biochemistry/Molecular Biology, Mayo Clinic/Foundation, Rochester, 55905, MN, USA

Haojie Huang, Ofelia L Zegarra-Moro, Douglas Benson & Donald J Tindall Authors * Haojie Huang View author publications You can also search for this author inPubMed Google Scholar *

Ofelia L Zegarra-Moro View author publications You can also search for this author inPubMed Google Scholar * Douglas Benson View author publications You can also search for this author

inPubMed Google Scholar * Donald J Tindall View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Donald J Tindall.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Huang, H., Zegarra-Moro, O., Benson, D. _et al._ Androgens repress Bcl-2 expression via activation of the

retinoblastoma (RB) protein in prostate cancer cells. _Oncogene_ 23, 2161–2176 (2004). https://doi.org/10.1038/sj.onc.1207326 Download citation * Received: 07 August 2003 * Revised: 29

October 2003 * Accepted: 30 October 2003 * Published: 15 December 2003 * Issue Date: 18 March 2004 * DOI: https://doi.org/10.1038/sj.onc.1207326 SHARE THIS ARTICLE Anyone you share the

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Nature SharedIt content-sharing initiative KEYWORDS * androgen receptor * Bcl-2 * RB * transcription regulation * prostate cancer