Authors: | Gao, S.; Lee, P.; Wang, H.; Gerald, W.; Adler, M.; Zhang, L.; Wang, Y. F.; Wang, Z. |
Article Title: | The androgen receptor directly targets the cellular Fas/FasL-associated death domain protein-like inhibitory protein gene to promote the androgen-independent growth of prostate cancer cells |
Abstract: | Androgens provide survival signals to prostate epithelial cells, and androgen ablation induces apoptosis in the prostate gland. However, the molecular mechanisms of actions of the androgen-signaling pathway in these processes are not fully understood. Here, we report that androgens induced expression of the cellular Fas/FasL-associated death domain protein-like inhibitory protein (c-FLIP) gene, which is a potent inhibitor of Fas/FasL-mediated apoptosis. The androgen receptor was recruited to the promoter of the c-FLIP gene in the presence of androgens. We found that c-FLIP promoter contained multiple functional androgen response elements. In addition, we show that c-FLIP overexpression accelerated progression to androgen independence by inhibiting apoptosis in LNCaP prostate tumors implanted in nude mice. Our results suggest that the androgen receptor affects survival and apoptosis of prostate cells through regulation of the c-FLIP gene in response to androgens. Copyright © 2005 by The Endocrine Society. |
Keywords: | survival; controlled study; human cell; promoter region; androgen; cancer growth; nonhuman; animal cell; mouse; animals; mice; animal tissue; gene targeting; gene overexpression; apoptosis; gene expression; fas antigen; molecular dynamics; animal experiment; animal model; mus musculus; prostatic neoplasms; gene expression regulation, neoplastic; molecular sequence data; membrane glycoproteins; oligonucleotide array sequence analysis; intracellular signaling peptides and proteins; cancer cell; base sequence; fas ligand protein; response elements; receptors, androgen; androgens; prostate carcinoma; casp8 and fadd-like apoptosis regulating protein; promoter regions (genetics); trans-activation (genetics) |
Journal Title: | Molecular Endocrinology |
Volume: | 19 |
Issue: | 7 |
ISSN: | 0888-8809 |
Publisher: | Endocrine Society |
Date Published: | 2005-07-01 |
Start Page: | 1792 |
End Page: | 1802 |
Language: | English |
DOI: | 10.1210/me.2004-0445 |
PUBMED: | 15731171 |
PROVIDER: | scopus |
PMCID: | PMC1855294 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 46" - "Export Date: 24 October 2012" - "CODEN: MOENE" - "Source: Scopus" |