EGF-INDUCED SIGNAL TRANSDUCTION IN CLONAL VARIANTS OF EPIDERMOID CARCINOMA A431
P. S. Grudinkin, V. V. Bagaeva, N. N. Nikol'sky
Institute of Cytology RAS, St. Petersburg;
e-mail: paulsg@mailcity.com
A431 epidermoid carcinoma cells have an increased expression of EGF receptor. In contrast to many other cell
lines and primary cells, these respond to EGF in high (more than 1 ng/ml) concentrations by cell cycle arrest,
apoptosis and detachment. Clonal variants of A431 (1a and 8a), able to grow in the presence of EGF in high
concentration, were previously developed in our laboratory (Gudkova, Sorokin, 1989). Here we tested upper pathways
of signal transduction from EGF receptor in the clonal variants, as compared to A431. We found no reasonable
difference in the expression of EGF receptor, as well as in its EGF-induced phosphorylation in A431 and clonal
variants. There were also no changes in the amount and activation of ERK MAP kinase in different cell lines.
In contrast, the amount of STAT1 transcription factor, known to play pro-apoptotic and antiproliferative roles,
was strictly diminished in both the clonal variants tested (1a and 8a), as compared to the parental line A431.
However, EGF-induced tyrosine phosphorylation of STAT1 decreased only in 8a. Increased phosphorylation of Akt
protein kinase, the key component of PI-3 kinase of the anti-apoptotic and proliferative signaling pathway, was
also observed in clonal variants. The data obtained demonstrate that resistance to EGF can be acquired in cells
having similar levels of EGF receptor expression and phosphorylation, but different in STAT1 or PI-3 kinase signal
transduction pathways. These pathways may presumably represent two antagonistic key elements regulating A431
proliferation and apoptosis.
Key words: A431 epidermoid carcinoma, clonal variants 1a and 8a, epidermal growth factor, STAT1
transcriptional factor
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