Stromal anti-apoptotic androgen receptor target gene c-FLIP in prostate cancer.
OBJECTIVE
The tumor microenvironment significantly influences prostate cancer progression. Androgen receptor exerts its effect through downstream target genes to regulate prostate cancer cell proliferation. The c-FLIP gene was recently shown to be an androgen receptor target gene. c-FLIP is an inactive homologue of caspase-8 and, thus, it inhibits the death receptor mediated apoptosis pathway. c-FLIP over expression was shown to accelerate the progression of prostate cancer cells to androgen independence. We evaluated the role of c-FLIP expression in stromal cells in prostate cancer development.


METHODS
We examined c-FLIP expression in 53 androgen dependent and 21 androgen independent prostate cancer stromal cells by immunohistochemical analysis. The effects of c-FLIP over expression in stromal cells on the growth and invasion of LNCaP and PC3 prostate cancer cells were determined in indirect coculture systems.


RESULTS
At the androgen dependent stage the stromal c-FLIP level was increased in prostate cancer tissue. The expression level of stromal c-FLIP was associated with tumor differentiation. However, stromal c-FLIP expression was not increased in androgen independent human prostate cancer. c-FLIP over expression in stromal cells stimulated the growth and invasion of prostate cancer, including LNCaP and PC3 cells in vitro.


CONCLUSIONS
These results indicate the over expression of stromal c-FLIP and its function for promoting prostate cancer growth and invasion.
Ye
Huihui
H
Department of Pathology and Urology, New York University School of Medicine, New York Harbor Healthcare System, New York, New York 10010, USA.
Li
Yirong
Y
Melamed
Jonathan
J
Pearce
Patrice
P
Wei
Jianjun
J
Chiriboga
Luis
L
Wang
Zhengxin
Z
Osman
Iman
I
Lee
Peng
P
D000368:Aged; D000728:Androgens / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein