OVEREXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN PANCREATIC-CANCER IS ASSOCIATED WITH CONCOMITANT INCREASES IN THE LEVELS OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA
OVEREXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN PANCREATIC-CANCER IS ASSOCIATED WITH CONCOMITANT INCREASES IN THE LEVELS OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA
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DOI：
10.1172/jci116001
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发表时间：
1992-10-01
影响因子：
15.9
通讯作者：
BEGER, HG
中科院分区：
文献类型：
--
作者：
KORC, M;CHANDRASEKAR, B;BEGER, HG
表皮生长因子（EGF）受体由EGF和转化生长因子-α（TGF-α）激活。使用免疫组织化学和免疫印迹技术，我们现在报告说，EGF受体，EGF和TGF-α在正常人胰腺的胰腺腺泡和导管中发现，并且所有三种蛋白质在人胰腺癌组织中以更高的水平表达。使用原位杂交技术，我们还报告了编码EGF受体，EGF和TGF-α的mRNA与其各自的蛋白质共定位。总RNA的北方印迹分析表明，与正常胰腺相比，胰腺肿瘤显示编码EGF受体、EGF和TGF-α的mRNA水平分别增加3倍、15倍和10倍。此外，通过原位杂交，在肿瘤块内这些mRNA部分显著增加。这些研究结果表明，EGF和TGF-α可能参与正常胰腺外分泌功能的调节，EGF受体及其两个主要配体的过度表达可能有助于人类胰腺癌中发生的病理生理过程。
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.