Regulation of mRNA and protein levels of β1 integrin variants in human prostate carcinoma

Elda Perlino, Mariarosaria Lovecchio, Rosa A. Vacca, Mara Fornaro, Loredana Moro, Pasquale Ditonno, Michele Battaglia, Francesco P. Selvaggi, Mauro G. Mastropasqua, Pantaleo Bufo, Lucia R. Languino

Research output: Contribution to journalArticle

Abstract

Alterations of integrin expression levels in cancer cells correlate with changes in invasiveness, tumor progression, and metastatic potential. The β1C integrin, an alternatively spliced form of the human β1 integrin, has been shown to inhibit prostate cell proliferation. Furthermore, β1C 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 β1C and β1 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 β1C mRNA is expressed in normal prostate and is significantly down-regulated in neoplastic prostate specimens. In addition, using a probe that hybridizes with all β1 variants, mRNA levels of β1 are found reduced in neoplastic versus normal prostate tissues. We demonstrate that β1C mRNA down-regulation does not correlate with either tumor grade or differentiation according to Gleason's grade and TNM system evaluation, and that β1C mRNA levels are not affected by hormonal therapy. In parallel, β1C protein levels were analyzed. As expected, β1C is found to be expressed in normal prostate and dramatically reduced in neoplastic prostate tissues; in contrast, using an antibody to β1 that recognizes all β1 variants, the levels of β1 are comparable in normal and neoplastic prostate, thus indicating a selective down-regulation of the β1C protein in prostate carcinoma. These results demonstrate for the first time that β1C and β1 mRNA expression is down-regulated in prostate carcinoma, whereas only β1C protein levels are reduced. Our data highlight a selective pressure to reduce the expression levels of β1C, a very efficient inhibitor of cell proliferation, in prostate malignant transformation.

Original languageEnglish
Pages (from-to)1727-1734
Number of pages8
JournalAmerican Journal of Pathology
Volume157
Issue number5
Publication statusPublished - 2000

    Fingerprint

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Perlino, E., Lovecchio, M., Vacca, R. A., Fornaro, M., Moro, L., Ditonno, P., Battaglia, M., Selvaggi, F. P., Mastropasqua, M. G., Bufo, P., & Languino, L. R. (2000). Regulation of mRNA and protein levels of β1 integrin variants in human prostate carcinoma. American Journal of Pathology, 157(5), 1727-1734.