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.
authors.affiliation: Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 173, Houston, TX 77030-4009, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.forename: Michael
authors.initials: M
authors.lastname: Adler
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D000728:Androgens; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C506387:Cflar protein, mouse; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011944:Receptors, Androgen
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