부산대학교 도서관

Epidermal growth factor receptor (EGFR) signaling has a central role in the regenerative response of the liver upon injury and is involved in cellular transformation linked to chronic damage. Hepatic EGFR expression, trafficking, and signaling are regulated by growth hormone (GH). Chronically elevated GH levels are associated with liver cancer development and progression in mice. Studies in different in vivo experimental models indicate that EGF and GH mutually crossregulate in a complex manner. Several factors, such as the extent of exposure to supraphysiological GH levels and the pattern of GH administration, are important variables to be considered in exploring the interplay between the two hormones in connection with the progression of hepatic tumors. Although growth hormone (GH) and epidermal growth factor (EGF) exert important physiological functions in the liver, chronic exposure to high GH levels and EGF receptor (EGFR) dysregulation are associated with tumorigenesis. Transgenic mice overexpressing GH display a high incidence of hepatic tumors. EGFR has a major role in the development of hepatocarcinoma. GH modulates the expression, trafficking, and signaling of the EGFR in various cell types, and this may represent a mechanism of liver tumor development. A major finding of our studies is that exposure to chronically high GH levels induces desensitization of EGFR-induced signaling in the liver, whereas administration of exogenous GH is not associated with this negative regulation. The pattern of circulating GH, sex, and the duration of the treatment appear to be major factors in determining the levels and activity of EGFR in hepatocytes. [ABSTRACT FROM AUTHOR]