Aj. Dicker et al., Functional characterization of cultured cells derived from an intraepidermal carcinoma of the skin (IEC-1), EXP CELL RE, 258(2), 2000, pp. 352-360
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.