Functional characterization of cultured cells derived from an intraepidermal carcinoma of the skin (IEC-1)

We have successfully isolated a cell line (IEC-1) from an intraepidermal ca rcinoma of the skin of a patient and compared its behavior, in vitro, to no rmal human epidermal keratinocytes (HEK) and squamous cell carcinoma cell l ines (SCCs), HEK differentiation comprises an initial growth arrest followe d by an induction of squamous differentiation-specific genes such as transg lutaminase type 1 (TG-1). Using thymidine uptake and TG-1 induction as mark ers of proliferation and differentiation, respectively, we were able to sho w that HEKs and the IEC-1 cells undergo growth arrest and induce TG-1 mRNA expression in response to various differentiation-inducing stimuli, while n eoplastic SCC cell lines did not, However, differentiation in HEKs was an i rreversible process whereas differentiation of the IEC-1 cells was reversib le. Furthermore, growth of IEC-1 cells in organotypic raft cultures reveale d differences in their ability to complete a squamous differentiation progr am compared with that of normal HEKs. The IEC-1 cells also exhibited a tran sitional phenotype with respect to replicative lifespan; HEKs had a lifespa n of 4-6 passages, IEC-1 cells of 15-17 passages, and SCC cells were immort al. These alterations in IEC-1 cell behavior were not associated with funct ional inactivation or mutations of the p53 gene. These data indicate that t he IEC-1 cells, derived from a preneoplastic skin tumor, exhibit difference s in their ability to undergo terminal differentiation and have an extended replicative lifespan. (C) 2000 Academic Press.