Androgen receptor expression in prostate carcinoma cells suppresses alpha6beta4 integrin-mediated invasive phenotype.
Prostate cancer cells may lose androgen-sensitivity after androgen ablation therapy, becoming highly invasive and metastatic. The biological mechanisms responsible for higher tumurogenicity of androgen-independent prostate carcinomas are not entirely known. We demonstrate that androgen receptor regulation of adhesion and invasion of prostate cancer cells through modulation of alpha6beta4 integrin expression may be one of the molecular mechanisms responsible of this phenomenon. We found that protein and gene expressions of alpha6 and beta4 subunits were strongly reduced in the androgen-sensitive cell line LNCaP respect to the androgen-independent PC3 and that transfection of PC3 cells with a full-length androgen receptor expression vector resulted in a decreased expression of alpha6beta4 integrin, reduced adhesion on laminin, and suppressed Matrigel invasion. Growth in soft agar was also suppressed in androgen receptor-positive PC3 clones. Treatment of androgen receptor positive clones with the synthetic androgen R1881 further reduced alpha6 and beta4 messenger RNA expression as well as adhesion on laminin and Matrigel invasion. Our results indicate that androgens regulate cell-extracellular matrix adhesion and invasion by modulation of integrin expression and function, thus keeping a low invasive phenotype of prostate cancer cells.
Bonaccorsi
L
L
Department of Clinical Physiopathology, University of Florence, Italy.
Carloni
V
V
Muratori
M
M
Salvadori
A
A
Giannini
A
A
Carini
M
M
Serio
M
M
Forti
G
G
Baldi
E
E
D000954:Antigens, Surface / Q000235:genetics*; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D039161:Integrin alpha6beta4; D016023:Integrins / Q000235:genetics*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D039161:Integrin alpha6beta4; D016023:Integrins; D008934:Mitogens; D011944:Receptors, Androgen