Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions

In-vitro and in-vivo studies have shown that autocrine growth factors and receptors are frequently expressed in human malignancies, Few of these studies, however, provide evidence that the identified autocrine pathway is functional, In this study, a functional autocrine growth pathway in pancreatic cancer has been identified using an in-vitro cell culture System. When pancreatic cancer cells were grown without change of medium, proliferation was greater than when either medium was replaced frequently (HPAF, CAPAN-2, PANC-1 or SW1990) or cells were grown in the presence of the EGF receltor tyrosine kinase inhibitor AG1478 or the MEK inhibitor PD098059 (HPAF or CAPAN-2). Activity of extracellurar-regulated kinases (ERK) 1 and 2 and c-jun and c-fos mRNA levels were significantly elevated in CAPAN-2 cells cultured continuously in serum-free medium, Collectively, the observations indicate that the EGF receptor and the ERK MAP kinase pathway mediate autocrine signals. In contrast to previous reports, the GRP and IGF-I receltors were shown not to be required for autocrine effects on pancreatic cancer cell proliferation, Autocrine stimulation of the EGF receltor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells.