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(American Journal of Pathology. 1998;153:1079-1087.)
© 1998 American Society for Investigative Pathology

Regular Articles

ß_1C Integrin in Epithelial Cells Correlates with a Nonproliferative Phenotype

Forced Expression of ß_1C Inhibits ProstateEpithelial Cell Proliferation

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

From the Department of Pathology,* Yale University School of Medicine, New Haven, Connecticut; Department of Pathology, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy; and Cancer Research Center, The Burnham Institute, La Jolla, California

The expression of the ß_1C integrin, an alternatively spliced variant of the ß₁ subunit, was investigated in human adult and fetal tissues. In the adult, ß_1C immunoreactivity was found in nonproliferative, differentiated simple, and/or pseudostratified epithelia in prostate glands and liver bile ducts. In contrast, ß_1C was undetectable in stratified squamous epithelium of the epidermis and/or in hepatocytes. Luminal prostate epithelial cells expressed ß_1C in vivo and in vitro, but no ß_1C was seen in basal cells, which are proliferating cells. Fetal prostate expressed ß_1C in differentiated glands that had a defined lumen, but not in budding glands, indicating that ß_1C is a marker of prostate epithelium differentiation. The ß_1C and the common ß_1A variants are differentially distributed: ß_1A was found in luminal and basal epithelial as well as in stromal cells in the prostate. In the liver, ß_1C and ß_1A were coexpressed in biliary epithelium, whereas vascular cells expressed only ß_1A. Because we found ß_1C in nonproliferative and differentiated epithelium, we investigated whether ß_1C could have a causal role in inhibiting epithelial cell proliferation. The results showed that exogenous expression of a ß_1C, but not of a ß_1A, cytoplasmic domain chimeric construct, completely inhibited thymidine incorporation in response to serum by prostate cancer epithelial cells. Consistent with these in vitro results, ß_1C appeared to be downregulated in prostate glands that exhibit regenerative features in benign hyperplastic epithelium. These data show that the presence of ß_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.

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