Hepatoma-derived growth factor involved in the carcinogenesis of gastric epithelial cells through promotion of cell proliferation by Erk1/2 activation

Hepatoma-derived growth factor (HDGF) is related to tumorigenesis and the development of cancer; it is an independent factor associated with the prognosis of liver cancer, non-small cell lung cancer and pancreatic cancer. However, the molecular mechanism by which HDGF participates in gastric carcinogenesis and development as well as its functional regulation during the development of gastric precancerous lesions needs to be further analyzed. In the present study, we analyzed the effect of HDGF transfection on the proliferation and on the changes of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-kappa B (NF-kappa B) pathways in gastric cancer AGS cells. HDGF transfection significantly activated Erk1/2 in AGS cells and promoted anchorage-independent growth. Further studies showed that HDGF expression gradually increased in the gastric carcinogenesis process and HDGF showed a high expression in poorly differentiated adenocarcinoma prone to lymphoid metastasis; these findings suggest that HDGF is involved in the gastric carcinogenesis process and promotes proliferation and metastasis via Erk1/2 activation. (Cancer Sci 2008; 99: 2120-2127).