Cell Growth & Differentiation, Vol 1, Issue 8 351-359, Copyright © 1990 by American Association of Cancer Research
Regulation of the epidermal growth factor receptor gene expression in a morphological variant isolated from an epidermal growth factor receptor-deficient small cell lung carcinoma cell line
S Gamou, Y Shimosato and N Shimizu
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.
Most cell lines derived from small cell lung carcinoma grow in an
anchorage-independent manner; they neither possess epidermal growth factor
binding activity nor express epidermal growth factor receptor (EGFR) mRNA.
A variant AD320, which grew in an anchorage-dependent manner with altered
morphology, was isolated from the small cell lung carcinoma cell line Lu134
by treatment with the demethylating agent 5-azacytidine. The analysis,
using methylation-sensitive restriction enzymes, revealed that the
methylation pattern was altered only in the structural region of the EGFR
gene; EGFR mRNA and epidermal growth factor binding activity could be
detected in the variant. In addition, drastic changes in gene expression
including a decrease of creatine kinase B mRNA and an increase of c-myc
mRNA were observed. The EGFR in the variant appeared to be an active part
of the transmembrane signaling machinery since c-fos and c-jun mRNA
accumulated after epidermal growth factor treatment, followed by EGFR and
c-myc mRNA accumulation. A potent tumor promoter,
12-O-tetradecanoylphorbol-13-acetate, also induced EGFR mRNA. Thus, the
inducible regulatory mechanism for the EGFR gene was activated in the
variant even though the EGFR gene was constitutively expressed.