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PMID: 11016951 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 21 ·2000-10-10 ·Pages 11256-61

Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C

Abstract

Although mutations of the breast cancer susceptibility gene 1 (BRCA1) may play important roles in breast and prostate cancers, the detailed mechanism linking the functions of BRCA1 to these two hormone-related tumors remains to be elucidated. Here, we report that BRCA1 interacts with androgen receptor (AR) and enhances AR target genes, such as p21((WAF1/CIP1)), that may result in the increase of androgen-induced cell death in prostate cancer cells. The BRCA1-enhanced AR transactivation can be further induced synergistically with AR coregulators, such as CBP, ARA55, and ARA70. Together, these data suggest that the BRCA1 may function as an AR coregulator and play positive roles in androgen-induced cell death in prostate cancer cells and other androgen/AR target organs.

MeSH Terms
Androgens/physiology BRCA1 Protein/physiology Cell Death/physiology Cyclin-Dependent Kinase Inhibitor p21 Cyclins/genetics Glutathione Transferase/metabolism Humans Male Prostatic Neoplasms/enzymology,pathology Receptors, Androgen/genetics Transcriptional Activation/physiology
Chemicals
Androgens BRCA1 Protein CDKN1A protein, human Cyclin-Dependent Kinase Inhibitor p21 Cyclins Receptors, Androgen Glutathione Transferase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yeh S
George Whipple Laboratory for Cancer Research, Departments of Urology, Pathology, Radiation Oncology, Biochemistry, Toxicology, and The Cancer Center, University of Rochester, Rochester, NY 14642, USA.
Hu Y C
Rahman M
Lin H K
Hsu C L
Ting H J
Kang H Y
Chang C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.190353897
Published
2000-10-10
Pages
11256-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17187
Subset
IM
Grants
NCI NIH HHS · T32 CA009363 · United States
NCI NIH HHS · CA55639 · United States
NCI NIH HHS · CA71570 · United States
NCI NIH HHS · T32 CA09363D · United States
External Links
PubMed source DOI: 10.1073/pnas.190353897 PMC Full Text View journal details
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