Overexpression of transforming growth factor-alpha and epidermal growth factor receptor, but not epidermal growth factor, in exocrine pancreatic tumours in hamsters.
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.
Visser
C J
CJ
Department of Pathology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Bruggink
A H
AH
Korc
M
M
Kobrin
M S
MS
de Weger
R A
RA
Seifert-Bock
I
I
van Blokland
W T
WT
van Garderen-Hoetmer
A
A
Woutersen
R A
RA
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D002273:Carcinogens; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008647:Mesocricetus; D009602:Nitrosamines; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism
D002273:Carcinogens; D009602:Nitrosamines; D016211:Transforming Growth Factor alpha; C013622:nitrosobis(2-oxopropyl)amine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors