Autocrine growth signal in human salivary gland adenocarcinoma cell line.

人唾液腺腺癌细胞系（HSG）在分子量为46 kDa的表皮生长因子（EGF）样分子介导下自主增殖。研究了该分子的受体。候选EGF受体和EGF受体家族成员c-erbB2产物在HSG细胞中共表达。46 kDa EGF-like分子与EGF受体结合，而不与c-erbB2产物结合，表明EGF受体是真正的EGF-like分子受体。EGF的磷酸化信号随后通过对外源性EGF高度负责的HSG AZA3细胞进行检测。酪氨酸特异性自磷酸化发生在EGF受体c端，随后MAP激酶和核转录因子Fos被激活。糖皮质激素和视黄酸通过其受体在HSG细胞中表达介导自分泌生长。为了明确视黄酸受体在HSG细胞中的转录活性，我们进行了转染实验。将含有维甲酸应答元件和胸苷激酶启动子的荧光素酶报告基因转染HSG细胞后，可诱导配体依赖性转激活，提示内源性维甲酸受体在体内具有调节靶基因表达的生理作用。分化诱导剂二丁基cAMP抑制HSG细胞生长。该化合物的信号似乎介导了蛋白激酶A级联并调节了EGF受体的表达。

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.