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• W1512884080 abstract "6126 Androgenic hormones play a central role in prostate cancer development and progression. They mediate their physiological effects by binding to the androgen receptor (AR), a nuclear transcription factor that induces the expression of genes responsible for prostate cancer growth. Identifying the genes critically involved in hormone stimulated cancer growth could lead to new potential targets and more effective therapies. We have recently demonstrated that GREB1 is an estrogen responsive gene that plays a pivotal role in estrogen stimulated breast cancer growth. Analysis of the putative GREB1 gene promoter identified multiple putative response elements for several hormones including estrogen, glucocorticoid, and androgen. The later led us to hypothesize that GREB1 is a novel androgen regulated gene involved in hormone dependant prostate cancer growth. Using real-time PCR we characterized the expression of GREB1 in response to androgen treatment in the hormone dependant prostate cancer cell line LNCap. Exogenous hormones were removed from the culture medium before exposing the cells for 24 hours to either the AR agonist R1881, or the estrogen receptor (ER) agonist 17 β-estradiol (E2), alone or in combination with receptor antagonists. GREB1 mRNA was induced by R1881 in a dose dependant manner to a maximum of 5-fold over control at 10-8 M. The AR antagonist casodex was able to block this induction. Similar results were seen with testosterone (TS) treatment. High dose E2 also induced GREB1 in the LNCap cells and this induction was blocked by either casodex or the ER antagonist ICI 182,780. These results are consistent with the fact that LNCaps express a mutated form of AR capable of binding estrogens at high concentrations. Changes in GREB1 expression levels were correlated with changes in cellular proliferation and cell cycle distribution. GREB1 androgen responsivity was confirmed using the ER - / AR + breast cancer cell line MDA-MB-453. Cells treated with dihydrotestosterone (DHT) and showed 3 fold induction of GREB1 at 10-8 M. Androgen treatment (R1881, TS or DHT) of the ER + / AR - negative breast cancer cell lines BT-474 and T47D did not result in GREB1 induction in spite of robust induction by E2. In contrast, TS did induced expression of GREB1 in the ER + / AR - cell line MCF-7, however, this induction was completely abrogated by the addition of letrozole suggesting the induction was due to aromatization of TS to estrogen in these cells. Our results show that GREB1 is a novel androgen regulated gene and we speculate that it may play a role in androgen induced prostate cancer growth, given its pivotal role in estrogen stimulated proliferation. Studies are currently underway to investigate this possibility using siRNA mediated knock down of GREB1 expression in androgen responsive cells." @default.
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• W1512884080 date "2005-05-01" @default.
• W1512884080 modified "2023-09-24" @default.
• W1512884080 title "GREB1 is a novel androgen regulated gene in prostate cancer" @default.
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