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Simple Epithelial Nature of Some Simian Virus-40-transformed Human Epidermal Keratinocytes¹

Departments of Dermatology [T. S. H., T-T. S.], Pharmacology [T. S. H., T-T. S.], and Pathology [M. L. S., V. D.], Rita and Stanley H. Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016

Previous studies have indicated that some Simian-virus-40-transformed human epidermal keratinocytes (SV40-HE) undergo significant changes in their growth and differentiated properties. To better understand the significance of these changes, we have characterized the keratins of SV40-HE cells by one- and two-dimensional immunoblot analysis using the subfamily-specific AE1 and AE3 monoclonal antikeratin antibodies. The results indicate that our SV40-HE cells have lost the M_r 58,000 (No. 5), M_r 56,000 (No. 6), M_r 50,000 (No. 14/15), M_r 48,000 (No. 16), and M_r 46,000 (No. 17) keratins that are expressed by cultured normal human keratinocytes. Instead, these cells express mainly M_r 52,000 (No. 8), M_r 45,000 (No. 18), and M_r 40,000 (No. 19) keratins, a set highly characteristic of simple epithelial cells. Furthermore, our SV40-HE cells have ceased to express involucrin, another marker for keratinocytes, and have a greatly diminished ability to undergo in vitro stratification. These results suggest that epidermal cells can sometimes lose their keratinocyte features as a consequence of viral transformation. This finding may have important implications regarding the mechanisms of epithelial differentiation and tumorigenesis and in the use of keratinocyte markers for tumor diagnosis.

¹ This investigation was aided in part by grants from the NIH (EY 4722, AM 34511, CA 16239 and CA 27869), and the Gillette Company.

² Supported by a National Research Service Award Institutional Training grant (5-T32-AM 7190).

³ Recipient of a NIH Research Career Development Award (EY 125) and a Monique Weill-Caulier Career Scientist Award. To whom requests for reprints should be addressed, at Department of Dermatology, New York University School of Medicine, 550 First Ave., New York, NY 10016.

Received 5/ 9/84. Accepted 8/20/84.

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