Visser C J, de Weger R A, van Blokland W T, Seifert-Bock I, Kobrin M S, Korc M, Woutersen R A
TNO Nutrition and Food Research Institute, Department of Pathology, Zeist, The Netherlands.
Br J Cancer. 1996 Jul;74(1):92-8. doi: 10.1038/bjc.1996.321.
In the present study, the expression of the epidermal growth factor receptor (EGFR) was investigated in putative preneoplastic and neoplastic acinar cell lesions induced in the rat pancreas by azaserine, using Northern blotting, in situ hybridisation (ISH) and immunohistochemistry. EGFR protein levels were decreased in putative preneoplastic eosinophilic acinar cell lesions (atypical acinar cell nodules, AACN) in comparison with normal acinar cells of the pancreas. However, EGFR mRNA expression correlated positively with the volume of AACN in pancreatic homogenates and ISH showed equal or stronger EGFR mRNA expression in AACN than in the surrounding normal acinar cells. Neither EGFR protein nor EGFR mRNA was detected in more advanced lesions such as acinar adenocarcinomas (in situ). Moreover, EGFR protein expression showed an inverse relationship with the mitotic rate of the acinar cells. These findings suggest that down-regulation of EGFR at the protein level may abrogate negative constraints on cell growth, which may stimulate the development of putative preneoplastic AACN to more advanced lesions and, ultimately, acinar adenocarcinomas.
在本研究中,利用Northern印迹法、原位杂交(ISH)和免疫组织化学,研究了用氮杂丝氨酸在大鼠胰腺中诱导产生的假定癌前和肿瘤性腺泡细胞病变中表皮生长因子受体(EGFR)的表达。与胰腺正常腺泡细胞相比,假定癌前嗜酸性腺泡细胞病变(非典型腺泡细胞结节,AACN)中的EGFR蛋白水平降低。然而,EGFR mRNA表达与胰腺匀浆中AACN的体积呈正相关,ISH显示AACN中的EGFR mRNA表达与周围正常腺泡细胞中的相等或更强。在更晚期的病变如腺泡腺癌(原位)中未检测到EGFR蛋白和EGFR mRNA。此外,EGFR蛋白表达与腺泡细胞的有丝分裂率呈负相关。这些发现表明,EGFR在蛋白水平的下调可能消除对细胞生长的负性限制,这可能刺激假定癌前AACN发展为更晚期病变,并最终发展为腺泡腺癌。