Beta1C integrin in epithelial cells correlates with a nonproliferative phenotype: forced expression of beta1C inhibits prostate epithelial cell proliferation

The expression of the beta1C integrin, an alternatively spliced variant of the beta1 subunit, was investigated in human adult and fetal tissues. In the adult, beta1C immunoreactivity was found in nonproliferative, differentiated simple, and/or pseudostratified epithelia in prostate glands and liver bile ducts. In contrast, beta1C was undetectable in stratified squamous epithelium of the epidermis and/or in hepatocytes. Luminal prostate epithelial cells expressed beta1C in vivo and in vitro, but no beta1C was seen in basal cells, which are proliferating cells. Fetal prostate expressed beta1C in differentiated glands that had a defined lumen, but not in budding glands, indicating that beta1C is a marker of prostate epithelium differentiation. The beta1C and the common beta1A variants are differentially distributed: beta1A was found in luminal and basal epithelial as well as in stromal cells in the prostate. In the liver, beta1C and beta1A were coexpressed in biliary epithelium, whereas vascular cells expressed only beta1A. Because we found beta1C in nonproliferative and differentiated epithelium, we investigated whether beta1C could have a causal role in inhibiting epithelial cell proliferation. The results showed that exogenous expression of a beta1C, but not of a beta1A, cytoplasmic domain chimeric construct, completely inhibited thymidine incorporation in response to serum by prostate cancer epithelial cells. Consistent with these in vitro results, beta1C appeared to be downregulated in prostate glands that exhibit regenerative features in benign hyperplastic epithelium. These data show that the presence of beta1C 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.