Alterations of integrin expression levels in cancer cells correlate with changes in invasiveness, tumor progression, and metastatic potential. The b1C integrin, an alternatively spliced form of the human b1 integrin, has been shown to inhibit prostate cell proliferation. Furthermore, b1C protein levels were found to be abundant in normal prostate glandular epithelium and down-regulated in prostatic adenocarcinoma. To gain further insights into the molecular mechanisms underlying abnormal cancer cell proliferation, we have studied b1C and b1 integrin expression at both mRNA and protein levels by Northern and immunoblotting analysis using freshly isolated neoplastic and normal human prostate tissue specimens. Steady-state mRNA levels were evaluated in 38 specimens: 33 prostatic adenocarcinomas exhibiting different Gleason's grade and five normal tissue specimens that did not show any histological manifestation of benign prostatic hypertrophy. Our results demonstrate that b1C mRNA is expressed in normal prostate and is significantly down-regulated in neoplastic prostate specimens. In addition, using a probe that hybridizes with all b1 variants, mRNA levels of b1 are found reduced in neoplastic versus normal prostate tissues. We demonstrate that b1C mRNA down-regulation does not correlate with either tumor grade or differentiation according to Gleason's grade and TNM system evaluation, and that b1C mRNA levels are not affected by hormonal therapy. In parallel, b1C protein levels were analyzed. As expected, b1C is found to be expressed in normal prostate and dramatically reduced in neoplastic prostate tissues; in contrast, using an antibody to b1 that recognizes all b1 variants, the levels of b1 are comparable in normal and neoplastic prostate, thus indicating a selective down-regulation of the b1C protein in prostate carcinoma. These results demonstrate for the first time that b1C and b1 mRNA expression is down-regulated in prostate carcinoma, whereas only b1C protein levels are reduced. Our data highlight a selective pressure to reduce the expression levels ofb1C, a very efficient inhibitor of cell proliferation, in prostate malignant transformation. (Am J Pathol 2000, 157:1727-1734)
Regulation of mRNA and protein levels of beta1 integrin variants in human prostate carcinoma
Perlino E;Vacca RA;
2000
Abstract
Alterations of integrin expression levels in cancer cells correlate with changes in invasiveness, tumor progression, and metastatic potential. The b1C integrin, an alternatively spliced form of the human b1 integrin, has been shown to inhibit prostate cell proliferation. Furthermore, b1C protein levels were found to be abundant in normal prostate glandular epithelium and down-regulated in prostatic adenocarcinoma. To gain further insights into the molecular mechanisms underlying abnormal cancer cell proliferation, we have studied b1C and b1 integrin expression at both mRNA and protein levels by Northern and immunoblotting analysis using freshly isolated neoplastic and normal human prostate tissue specimens. Steady-state mRNA levels were evaluated in 38 specimens: 33 prostatic adenocarcinomas exhibiting different Gleason's grade and five normal tissue specimens that did not show any histological manifestation of benign prostatic hypertrophy. Our results demonstrate that b1C mRNA is expressed in normal prostate and is significantly down-regulated in neoplastic prostate specimens. In addition, using a probe that hybridizes with all b1 variants, mRNA levels of b1 are found reduced in neoplastic versus normal prostate tissues. We demonstrate that b1C mRNA down-regulation does not correlate with either tumor grade or differentiation according to Gleason's grade and TNM system evaluation, and that b1C mRNA levels are not affected by hormonal therapy. In parallel, b1C protein levels were analyzed. As expected, b1C is found to be expressed in normal prostate and dramatically reduced in neoplastic prostate tissues; in contrast, using an antibody to b1 that recognizes all b1 variants, the levels of b1 are comparable in normal and neoplastic prostate, thus indicating a selective down-regulation of the b1C protein in prostate carcinoma. These results demonstrate for the first time that b1C and b1 mRNA expression is down-regulated in prostate carcinoma, whereas only b1C protein levels are reduced. Our data highlight a selective pressure to reduce the expression levels ofb1C, a very efficient inhibitor of cell proliferation, in prostate malignant transformation. (Am J Pathol 2000, 157:1727-1734)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.