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

Abstract

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 receptor tyrosine 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 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 receptors were shown not to be required for autocrine effects on pancreatic cancer cell proliferation. Autocrine stimulation of the EGF receptor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells. © 2001 Cancer Research Campaign http://www.bjcancer.com

Overexpression of CEACAM6 promotes insulin-like growth factor I-induced pancreatic adenocarcinoma cellular invasiveness

“…Furthermore, in order to minimize any potentially confounding effects on cellular proliferation induced by autocrine growth factors, we performed the proliferation assays with 8-hourly medium changes. Similar approaches have been shown to prevent autocrine growth factor-induced proliferation in Capan2 pancreatic adenocarcinoma cells (Murphy et al, 2001). Over the time period and at the IGF-I concentration of relevance to the invasion assay, we observed no significant difference in cellular proliferation among pIRES-CEA-CAM6.1, pIRES-CEACAM6.2, pIRES-eGFP transfectants and parental Capan2 cells (data not shown).…”

Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer

“…Pancreatic cancer like many other tumors has been shown to overexpress the epidermal growth factor receptor (EGFR) and/or its family members (2)(3)(4). Therefore, novel avenues by which EGFRs could be inactivated represent a promising strategy for the development of novel and selective anticancer therapies.…”

Epidermal growth factor induces adult human islet cell dedifferentiation

“…Finally, EGF signaling is also implicated in pancreatic carcinogenesis (Korc et al 1992, Murphy et al 2001, Miyamoto et al 2003. Here again, however, the mechanism of EGF is difficult to interpret, especially given that the cell of origin of pancreatic carcinogenesis remains a subject of debate.…”

“…With respect to cellular transformation, EGF signaling is linked to pancreatic adenocarcinoma (Korc et al 1992, Murphy et al 2001, Miyamoto et al 2003, characterized by expression of duct epithelial markers. There is debate as to the cell of origin (Pour et al 2003), suggesting that EGF signaling may again induce cellular dedifferentiation into a duct-like phenotype.…”