β1C integrin in epithelial cells correlates with a nonproliferative phenotype -: Forced expression of β1C inhibits prostate epithelial cell proliferation

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