Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger H G
Department of Medicine, University of California, Irvine 92717.
J Clin Invest. 1992 Oct;90(4):1352-60. doi: 10.1172/JCI116001.
The epidermal growth factor (EGF) receptor is activated by both EGF and transforming growth factor-alpha (TGF-alpha). Using immunohistochemical and immunoblotting techniques we now report that the EGF receptor, EGF, and TGF-alpha are found in both pancreatic acini and ducts in the normal human pancreas, and that all three proteins are expressed at higher levels in human pancreatic cancer tissues. Using in situ hybridization techniques, we also report that the mRNA encoding the EGF receptor, EGF, and TGF-alpha colocalize with their respective proteins. Northern blot analysis of total RNA indicates that, by comparison with the normal pancreas, the pancreatic tumors exhibit a 3-, 15-, and 10-fold increase in the mRNA levels encoding the EGF receptor, EGF, and TGF-alpha, respectively. Furthermore, by in situ hybridization, there is a marked increase in these mRNA moieties within the tumor mass. These findings suggest that EGF and TGF-alpha may participate in the regulation of normal pancreatic exocrine function, and that overexpression of the EGF receptor and its two principal ligands may contribute to the pathophysiological processes that occur in human pancreatic cancer.
表皮生长因子（EGF）受体可被EGF和转化生长因子-α（TGF-α）激活。我们利用免疫组织化学和免疫印迹技术，现报道在正常人类胰腺的腺泡和导管中均发现了EGF受体、EGF和TGF-α，且这三种蛋白在人类胰腺癌组织中的表达水平均更高。利用原位杂交技术，我们还报道了编码EGF受体、EGF和TGF-α的mRNA与其各自的蛋白共定位。对总RNA的Northern印迹分析表明，与正常胰腺相比，胰腺肿瘤中编码EGF受体、EGF和TGF-α的mRNA水平分别增加了3倍、15倍和10倍。此外，通过原位杂交发现，肿瘤块内这些mRNA部分显著增加。这些发现提示EGF和TGF-α可能参与正常胰腺外分泌功能的调节，且EGF受体及其两种主要配体的过表达可能促成人类胰腺癌中发生的病理生理过程。
