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

In-vitro and in-vivo studies have shown that autocrine growth factors and r eceptors are frequently expressed in human malignancies. Few of these studi es, however, provide evidence that the identified autocrine pathway is func tional. In this study, a functional autocrine growth pathway in pancreatic cancer has been identified using an in-vitro cell culture system. When panc reatic cancer cells were grown without change of medium. proliferation was greater than when either medium was replaced frequently (HPAF, CAPAN-2, PAN C-1 or SW1990) or cells were grown in the presence of the EGF receptor tyro sine kinase inhibitor AG1478 or the MEK inhibitor PD098059 (HPAF or CAPAN-2 ). Activity of extracellular-regulated kinases (ERK) 1 and 2 and c-jun and c-fos mRNA levels were significantly elevated in CAPAN-2 cells cultured con tinuously in serum-free medium. Collectively. the observations indicate tha t the EGF receptor and the ERK MAP kinase pathway mediate autocrine signals . In contrast to previous reports, the GRP and IGF-I receptors were shown n ot to be required for autocrine effects on pancreatic cancer cell prolifera tion. Autocrine stimulation of the EGF receptor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells. (C) 2001 Cancer Research Campaign.