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 BglII 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.