This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bowden, P. E. Articles by DiPaolo, J. A. Search for Related Content PubMed PubMed Citation Articles by Bowden, P. E. Articles by DiPaolo, J. A.

Down-Regulation of Keratin 14 Gene Expression after v-Ha-ras Transfection of Human Papillomavirus-immortalized Human Cervical Epithelial Cells

Laboratory of Biology, Division of Cancer Etiology, National Cancer Institute, NIH, Bethesda, Maryland 20892

Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed significantly from both normal and human papillomavirus (HPV) immortalized exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis and mRNA levels, was dramatically down-regulated in the cervical SCC lines while keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in an HPV-16 immortalized cervical cell line after tumorigenic transformation with recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also exhibited an altered keratin profile and the levels of K14 protein synthesis, as well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not significantly down-regulated. In addition, neoplastic cervical SCC lines exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down-regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different manner to exocervical cells. Transfection of human papillomavirus-immortalized epidermal keratinocytes with the Bg/II N fragment of herpes simplex virus 2 produced a neoplastic cell line, but K5 and K14 expression remained unchanged. Thus, neoplastic transformation of human exocervical cells, both in vivo (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical SCC), is accompanied by characteristic changes in keratin expression. The specific down-regulation of K14 in these tumorigenic cervical cells, in the absence of significant changes in the expression of K5, implies that the normal coordinate regulation of K5 and K14 gene expression has been uncoupled.

¹ Present address: Department of Dermatology, University of Wales College of Medicine, Heath Park, Cardiff, Wales CF4 4XN.

² Present address: Department of Obstetrics and Gynecology, Georgetown University Medical Center, 3800 Reservoir Road N. W., Washington, D.C. 20007.

³ To whom requests for reprints should be addressed.

Received 6/ 6/90. Accepted 8/21/92.

This article has been cited by other articles:

				K.-N. Zhao, W. Gu, N. X. Fang, N. A. Saunders, and I. H. Frazer Gene Codon Composition Determines Differentiation-Dependent Expression of a Viral Capsid Gene in Keratinocytes In Vitro and In Vivo Mol. Cell. Biol., October 1, 2005; 25(19): 8643 - 8655. [Abstract] [Full Text] [PDF]