Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells.
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.
Yeh
S
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
YC
Rahman
M
M
Lin
H K
HK
Hsu
C L
CL
Ting
H J
HJ
Kang
H Y
HY
Chang
C
C
D000728:Androgens / Q000502:physiology*; D019313:BRCA1 Protein / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics*; D015533:Transcriptional Activation / Q000502:physiology*
D000728:Androgens; D019313:BRCA1 Protein; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011944:Receptors, Androgen; D005982:Glutathione Transferase