Regulation of mRNA and protein levels of beta 1 integrin variants in humanprostate carcinoma

Alterations of integrin expression levels in cancer cells correlate with ch anges in invasiveness, tumor progression, and metastatic potential. The bet a 1C integrin, an alternatively spliced form of the human beta1 integrin, h as been shown to Inhibit prostate cell proliferation, Furthermore, beta 1C protein levels were found to be abundant in normal prostate glandular epith elium and down-regulated in prostatic adenocarcinoma, To gain further insig hts into the molecular mechanisms underlying abnormal cancer cell prolifera tion, we have studied beta 1C, and beta1 integrin expression at both mRNA a nd protein levels by Northern and immunoblotting analysis using freshly iso lated neoplastic and normal human prostate tissue specimens, Steady-state m RNA levels were evaluated in 38 specimens: 33 prostatic adenocarcinomas exh ibiting different Gleason's grade and five normal tissue specimens that did not show any histological manifestation of benign prostatic hypertrophy. O ur results demonstrate that beta 1C mRNA is expressed in normal prostate ac id is significantly down-regulated in neoplastic prostate specimens. In add ition, using a probe that hybridizes with all beta1 variants, mRNA levels o f beta1 are found reduced in neoplastic versus normal prostate tissues. We demonstrate that beta 1C mRNA down-regulation does not correlate with eithe r tumor grade or differentiation according to Gleason's grade and TNM syste m evaluation, and that beta 1C mRNA levels are not affected by hormonal the rapy. In parallel, beta 1C protein levels were analyzed. As expected, beta 1C is found to be expressed in normal prostate and dramatically reduced in neoplastic prostate tissues; in contrast, using an antibody to beta1 that r ecognizes all beta1 variants, the levels of beta1 are comparable in normal and neoplastic prostate, thus indicating a selective down-regulation of the beta 1C protein in prostate carcinoma. These results demonstrate for the f irst time that beta 1C and beta1 mRNA expression is down-regulated in prost ate carcinoma, whereas only beta 1C protein levels are reduced. Our data hi ghlight a selective pressure to reduce the expression levels of beta 1C, a very efficient inhibitor of cell proliferation, in prostate malignant trans formation.