[EGF-induced signal transduction in clonal cells of epidermoid carcinoma A431].
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.
Institute of Cytology RAS, St. Petersburg. paulsg@mailcity.com
P S
PS
Grudinkin
V V
VV
Bagaeva
N N
NN
Nikol'skiĭ
D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000187:drug effects* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine; C494079:STAT1 protein, human; C494918:AKT1 protein, human