Overexpression of transforming growth factor-α and epidermal growth factor receptor, but not epidermal growth factor, in exocrine pancreatic tumours in hamsters

Abstract

Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expression were studied in the pancreas of N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. After initiation pancreatic carcinogenesis was modulated by a high fat diet or by injections with the cholecystokinin analogue caerulein. Autopsies were performed 6 and 12 months after the last injection with BOP. Immunohistochemistry revealed a weak expression of TGF-alpha in nomal acinar cells and a stronger expression in ductular and centro-acinar cells. Over-expression of TGF-alpha was observed in advanced putative preneoplastic lesions (classified as borderline lesions) and in ductular adenocarcinomas. EGFR immunoreactivity was present only in ductular adenocarcinomas. EGF peptide expression was observed both in acinar and ductular normal and tumorous cells and the level of expression did not change significantly during carcinogenesis. Moreover, the post-initiation treatments did not cause differences in EGF, TGF-alpha or EGFR peptide or mRNA levels, except for a significantly lower expression of TGF-alpha mRNA in hamsters fed a high fat diet when compared with those fed a low fat diet. TGF-alpha mRNA levels increased, whereas EGF mRNA levels decreased significantly in total pancreatic homogenates of BOP-treated hamsters in comparison with untreated controls. Also, in ductular adenocarcinomas TGF-alpha and EGFR (but not EGF) mRNA levels were significantly higher than in normal pancreatic homogenates. In pancreatic homogenates obtained 6 months after the last BOP injection, these differences were less pronounced in comparison with those obtained after 12 months. The present results indicate that TGF-alpha (but not EGF) might act in a paracrine or autocrine manner in pancreatic tumours in BOP-treated hamsters via simultaneously expressed EGFR. However, TGF-alpha, EGF and EGFR do not seem to be involved in the modulating effects of a high fat diet or caerulein treatment on pancreatic carcinogenesis in BOP-treated hamsters.

Molecular mechanisms underlying Ca2+-mediated motility of human pancreatic duct cells

“…Pancreatic cancer is the fourth leading cause of cancerrelated death in the United States, and nearly all patients diagnosed with pancreatic cancer die from a cancer-related death (24,26,52), with a 3% 5-year survival rate following diagnosis (43). Metastases are common in the process, particularly to the lymph nodes and liver (9,19,61). Histopathological analysis shows a ductal histology that makes up Ͼ90% of the cases of pancreatic adenocarcinoma (50).…”

Assessing the role of the EGF receptor in the development and progression of pancreatic cancer

“…Correspondingly, PanIN lesions in a murine model of pancreatic cancer expressed TGFα, but not EGF. 42 In vitro experiments utilizing acinar explants revealed that TGFα-mediated EGFR activation promoted ADM via a Notch-dependent mechanism. 43,44 Additionally, expression of KRAS G12D promotes ADM both in vitro and in vivo, via an EGFR-dependent mechanism.…”

Pancreatic cancer in rats and hamsters does not induce IAPP-related hyperglycaemia

“…All animals were given standard laboratory chow until one week after the last injection. From that time onwards, AIN-76-based diets were provided (Visser et al, 1995(Visser et al, , 1996. All carcinogen-treated animals were assigned randomly to one of the following experimental sub-groups: regular diet (5% corn oil); regular diet plus s.c. injections of 2.5 µg/kg body weight caerulein, 3 times a week, or high-fat diet (20% corn oil), in isocaloric (rat) or non-isocaloric (hamster) form (Birt et al, 1989).…”