Visser C J, Bruggink A H, Korc M, Kobrin M S, de Weger R A, Seifert-Bock I, van Blokland W T, van Garderen-Hoetmer A, Woutersen R A
Department of Pathology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Carcinogenesis. 1996 Apr;17(4):779-85. doi: 10.1093/carcin/17.4.779.
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.
利用免疫组织化学、Northern印迹法和半定量PCR技术，研究了N-亚硝基双（2-氧代丙基）胺（BOP）处理的仓鼠胰腺中表皮生长因子（EGF）、转化生长因子-α（TGF-α）和表皮生长因子受体（EGFR）的表达。在启动胰腺癌发生后，通过高脂饮食或注射胆囊收缩素类似物蛙皮素对其进行调节。在最后一次注射BOP后6个月和12个月进行尸检。免疫组织化学显示，TGF-α在正常腺泡细胞中表达较弱，在导管和腺泡中心细胞中表达较强。在晚期假定的癌前病变（分类为临界病变）和导管腺癌中观察到TGF-α的过表达。EGFR免疫反应仅存在于导管腺癌中。在腺泡和导管正常及肿瘤细胞中均观察到EGF肽表达，且其表达水平在致癌过程中无显著变化。此外，启动后处理在EGF、TGF-α或EGFR肽或mRNA水平上未引起差异，除了与低脂饮食喂养的仓鼠相比，高脂饮食喂养的仓鼠中TGF-α mRNA表达显著降低。与未处理的对照组相比，BOP处理的仓鼠胰腺总匀浆中TGF-α mRNA水平升高，而EGF mRNA水平显著降低。同样，在导管腺癌中，TGF-α和EGFR（而非EGF）mRNA水平显著高于正常胰腺匀浆。在最后一次注射BOP后6个月获得的胰腺匀浆中，与12个月后获得的相比，这些差异不太明显。目前的结果表明，在BOP处理的仓鼠胰腺肿瘤中，TGF-α（而非EGF）可能通过同时表达的EGFR以旁分泌或自分泌方式发挥作用。然而，TGF-α、EGF和EGFR似乎不参与高脂饮食或蛙皮素处理对BOP处理的仓鼠胰腺癌发生的调节作用。
