Carcinogenesis, Vol 19, 683-686, Copyright © 1998 by Oxford University Press
Y Liu and MF Kulesz-Martin
We have developed a multistage model system in which a normal mouse
keratinocyte clone has been initiated with 7,12- dimethylbenz[a]anthracene
and variant clones derived with benign or malignant phenotypes. To identify
specific genes altered during mouse skin carcinogenesis, the gene
expression patterns of the normal parental epidermal cell, an initiated
cell, a benign papilloma, and a poorly differentiated squamous cell
carcinoma were compared using RNA differential display. Most alterations in
gene expression were observed at malignant conversion, that is, in the
poorly differentiated squamous cell carcinoma that is known to have
deregulated expression of p53. The sequence of a cloned cDNA fragment lost
in the poorly differentiated squamous cell carcinoma was nearly identical
to the 3' region of an adhesion-related kinase which is involved in
homophilic cell aggregation. It is found in normal epidermal progenitor
cells as well as tumorigenic cells with differentiation potential, but not
in tumorigenic cells with a poorly differentiated phenotype, suggesting
that this adhesion-related kinase may be involved in epidermal cell
differentiation. Differential display within the cloned epidermal cell
model appears to be useful in detecting and identifying malignant
conversion-associated genes which then can be tested directly for their
potential role in epithelial carcinogenesis.
ARTICLES
Altered gene expression in a clonal epidermal cell model of carcinogenesis identified by RNA differential display
Program of Biochemistry and Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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