GREB1 is a novel androgen-regulated gene required for prostate cancer growth.
BACKGROUND
Gene regulated in breast cancer 1 (GREB1) is a novel estrogen-regulated gene shown to play a pivotal role in hormone-stimulated breast cancer growth. GREB1 is expressed in the prostate and its putative promoter contains potential androgen receptor (AR) response elements.


METHODS
We investigated the effects of androgens on GREB1 expression and its role in androgen-dependent prostate cancer growth.


RESULTS
Real-time PCR demonstrated high level GREB1 expression in benign prostatic hypertrophy (BPH), localized prostate cancer (L-PCa), and hormone refractory prostate cancer (HR-PCa). Androgen treatment of AR-positive prostate cancer cells induced dose-dependent GREB1 expression, which was blocked by anti-androgens. AR binding to the GREB1 promoter was confirmed by chromatin immunoprecipitation (ChIP) assays. Suppression of GREB1 by RNA interference blocked androgen-stimulated LNCaP cell proliferation.


CONCLUSIONS
GREB1 is expressed in proliferating prostatic tissue and prostate cancer, is regulated by androgens, and suppression of GREB1 blocks androgen-induced growth suggesting GREB1 may be critically involved in prostate cancer proliferation.
Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. jimmyrae@umich.edu
James M
JM
Rae
Michael D
MD
Johnson
Kevin E
KE
Cordero
Joshua O
JO
Scheys
José M
JM
Larios
Marco M
MM
Gottardis
Kenneth J
KJ
Pienta
Marc E
ME
Lippman
D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000728:Androgens; D004273:DNA, Neoplasm; D004967:Estrogens; C416830:GREB1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering