Title
Overexpression of transforming growth factor-α and epidermal growth factor receptor, but not epidermal growth factor, in exocrine pancreatic tumours in hamsters
Author
Visser, C.J.T.
Bruggink, A.H.
Korc, M.
Kobrin, M.S.
de Weger, R.A.
Seifert-Bock, I.
van Blokland, W.T.M.
van Garderen Hoetmer, A.
Woutersen, R.A.
TNO Voeding
Publication year
1996
Abstract
Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-α (TGF-α) 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-α in normal acinar cells and a stronger expression in ductular and centro-acinar cells. Overexpression of TGF-α 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-α or EGFR peptide or mRNA levels, except for a significantly lower expression of TGF-α mRNA in hamsters fed a high fat diet when compared with those fed a low fat diet. TGF-α 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-α 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-α (but not EGF) might act in a paracrine or autocrine manner in pancreatic tumours in BOP-treated hamsters via simultaneously expressed EGFR. However, TGF-α, 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.
Subject
Nutrition
bis(2 oxopropyl)nitrosamine
ceruletide
epidermal growth factor
epidermal growth factor receptor
transforming growth factor alpha
acinar cell
animal experiment
animal model
animal tissue
article
carcinogenesis
controlled study
hamster
immunohistochemistry
lipid diet
nonhuman
northern blotting
pancreas adenocarcinoma
pancreas duct
pancreas tumor
polymerase chain reaction
precancer
priority journal
Adenocarcinoma
Animals
Blotting, Northern
Body Weight
Carcinogens
Cricetinae
Epidermal Growth Factor
Immunohistochemistry
Mesocricetus
Nitrosamines
Organ Size
Pancreas
Pancreatic Neoplasms
Polymerase Chain Reaction
Receptor, Epidermal Growth Factor
Transforming Growth Factor alpha
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DOI
https://doi.org/10.1093/carcin/17.4.779
TNO identifier
233266
ISSN
0143-3334
Source
Carcinogenesis, 17 (4), 779-785
Document type
article