Autocrine growth signal in human salivary gland adenocarcinoma cell line.

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Human salivary gland adenocarcinoma cell line (HSG) proliferates autonomously mediated by an epidermal growth factor (EGF)-like molecule with a molecular weight of 46 kDa. The receptor for this molecule was investigated. The candidates, EGF receptor and c-erbB2 product which is a member of EGF receptor family, were co-expressed in HSG cells. 46 kDa EGF-like molecule bound to EGF receptor but not to c-erbB2 product, which revealed that EGF receptor is a genuine receptor for EGF-like molecule. The phosphorylation signal by EGF was next examined by use of HSG AZA3 cells which have high responsibility to exogeneous EGF.Tyrosine-specific autophosphorylation occurred at C-terminal region of EGF receptor, and followed by the activation of MAP kinase and a nuclear transcription factor, Fos.The autocrine growth is mediated by glucocorticoid and retinoic acid via their receptors expressed in HSG cells. In order to clarify the transcriptional activity of retinoic acid receptor of HSG cells, transfection experiment was examined. When a luciferase reporter gene including a retinoic acid response element and thymidine kinase promoter was transfected to HSG cells, the ligand dependent transactivation was induced, suggesting that the endogeneous retinoic acid receptors have physiological roles in regulating target gene expression in vivo.Di-butyryl cAMP,a differentiation inducer, repressed HSG cell growth. The signal of this compound seemed to mediate protein kinase A cascade and regulate the EGF receptor expression.