Growth signaling by epidermal growth factor in the human salivary gland adenocarcinoma cell line.．

Abstract

The effect of epidermal growth factor (EGF) on cell proliferation was studied in HSG-AZA3, a subclone of human salivary gland adenocarcinoma cell line (HSG). The treatment with EGF, which is involved in cell growth, increased cell numbers and [³H]thymidine incorporation into DNA. In addition, stimulation of EGF enhanced both EGF receptor protein and EGF receptor mRNA levels. On the other hand, the treatment of HSG-AZA3 cells with EGF resulted in EGF-dependent tyrosine phosphorylation of EGF receptor, autophosphorylation, 5min after stimulation, followed by activation of MAP kinase which is one of the kinases invloved in the phosphorylation cascade. These findings indicate that MAP kinase received the signal from the membrane-bound EGF receptor. Moreover, the protooncogene product Fos, which acts as a transcription factor in the nuclei, was rapidly induced by EGF 1-3hr after stimulation. These results suggest that activation of EGF receptor-associated tyrosine kinase and MAP kinase may play an important role in the EGF signaling pathway, and that rapid induction of Fos be prerequisite for cellular proliferation of HSG-AZA3 cells.