OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR, BUT NOT EPIDERMAL GROWTH-FACTOR, IN EXOCRINE PANCREATIC TUMORS IN HAMSTERS

Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth fact or-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expre ssion 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 th e last injection with BOP. Immunohistochemistry revealed a weak expres sion of TGF-alpha in normal acinar cells and a stronger expression in ductular and centro-acinar cells, Overexpression of TGF-alpha was obse rved in advanced putative preneoplastic lesions (classified as borderl ine lesions) and in ductular adenocarcinomas. EGFR immunoreactivity wa s present only in ductular adenocarcinomas. EGF peptide expression was observed both in acinar and ductular normal and tumorous cells and th e level of expression did not change significantly during carcinogenes is, Moreover, the post-initiation treatments did not cause differences in EGF, TGF-alpha or EGFR peptide or mRNA levels, except for a signif icantly 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 level s increased, whereas EGF mRNA levels decreased significantly in total pancreatic homogenates of BOP-treated hamsters in comparison with untr eated controls, Also, in ductular adenocarcinomas TGF-alpha and EGFR ( but not EGF) mRNA levels were significantly higher than in normal panc reatic homogenates. In pancreatic homogenates obtained 6 months after the last BOP injection, these differences were less pronounced in comp arison with those obtained after 12 months, The present results indica te that TGF-alpha (but not EGF) might act in a paracrine or autocrine manner in pancreatic tumours in BOP-treated hamsters via simultaneousl y expressed EGFR. However, TGF-alpha, EGF and EGFR do not seem to be i nvolved in the modulating effects of a high fat diet or caerulein trea tment on pancreatic carcinogenesis in BOP-treated hamsters.