Androgen receptor expression in prostate carcinoma cells suppresses alpha 6 beta 4 integrin-mediated invasive phenotype

Prostate cancer cells may lose androgen-sensitivity after androgen ablation therapy, becoming highly invasive and metastatic. The biological mechanism s responsible for higher tumurogenicity of androgen-independent prostate ca rcinomas are not entirely known. We demonstrate that androgen receptor regu lation of adhesion and invasion of prostate cancer cells through modulation of alpha 6 beta 4 integrin expression may be one of the molecular mechanis ms responsible of this phenomenon. We found that protein and gene expressio ns of alpha 6 and beta 4 subunits were strongly reduced in the androgen-sen sitive cell line LNCaP respect to the androgen-independent PC3 and that tra nsfection of PC3 cells with a full-length androgen receptor expression vect or resulted in a decreased expression of alpha 6 beta 4 integrin, reduced a dhesion on laminin, and suppressed Matrigel invasion. Growth in soft agar w as also suppressed in androgen receptor-positive PC3 clones. Treatment of a ndrogen receptor positive clones with the synthetic androgen R1881 further reduced alpha 6 and beta 4 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.