β(1C) integrin in epithelial cells correlates with a nonproliferative phenotype: Forced expression of β(1C) inhibits prostate epithelial cell proliferation

Mara Fornaro, Michela Manzotti, Giovanni Tallini, Amy E. Slear, Silvano Bosari, Erkki Ruoslahti, Lucia R. Languino

Research output: Contribution to journalArticlepeer-review

Abstract

The expression of the β(1C) integrin, an alternatively spliced variant of the β1 subunit, was investigated in human adult and fetal tissues. In the adult, β(1C) immunoreactivity was found in nonproliferative, differentiated simple, and/or pseudostratified epithelia in prostate glands and liver bile ducts. In contrast, β(1C) was undetectable in stratified squamous epithelium of the epidermis and/or in hepatocytes. Luminal prostate epithelial cells expressed β(1C) in vivo and in vitro, but no β(1C) was seen in basal cells, which are proliferating cells. Fetal prostate expressed β(1C) in differentiated glands that had a defined lumen, but not in budding glands, indicating that β(1C) is a marker of prostate epithelium differentiation. The β(1C) and the common β(1A) variants are differentially distributed: β(1A) was found in luminal and basal epithelial as well as in stromal cells in the prostate. In the liver, β(1C) and β(1A) were coexpressed in biliary epithelium, whereas vascular cells expressed only β(1A). Because we found β(1C) in nonproliferative and differentiated epithelium, we investigated whether β(1C) could have a causal role in inhibiting epithelial cell proliferation. The results showed that exogenous expression of a β(1C), but not of a β(1A), cytoplasmic domain chimeric construct, completely inhibited thymidine incorporation in response to serum by prostate cancer epithelial cells. Consistent with these in vitro results, β(1C) appeared to be downregulated in prostate glands that exhibit regenerative features in benign hyperplastic epithelium. These data show that the presence of β(1C) integrins in epithelial cells correlates with a nonproliferative, differentiated phenotype and is growth inhibitory to prostate epithelial cells in vitro. These findings indicate a novel pathophysiological role for this integrin variant in epithelial cell proliferation.

Original languageEnglish
Pages (from-to)1079-1087
Number of pages9
JournalAmerican Journal of Pathology
Volume153
Issue number4
Publication statusPublished - Oct 1998

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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