Cartwright C A, Meisler A I, Eckhart W
Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1990 Jan;87(2):558-62. doi: 10.1073/pnas.87.2.558.
Colonic neoplasia provides an opportunity to study tumor progression because most carcinomas arise from adenomas (polyps), which, in turn, arise from normal epithelia. The malignant potential of adenomas varies with size, histology, and degree of dysplasia. Polyps that are less than 2 cm with villous architecture and severe dysplasia are most likely to contain carcinoma. Previous studies demonstrated that the in vitro protein-tyrosine kinase activity of pp60c-src from colon carcinomas is significantly higher than that from adjacent normal mucosa. Here we report that the protein kinase activity of pp60c-src is also elevated in colonic polyps. Activity is highest in malignant polyps and in greater than 2-cm benign polyps that contain villous structure and severe dysplasia. Thus, pp60c-src activation occurs in benign polyps that are at greatest risk for developing cancer. These data suggest that activation of the protooncogene product pp60c-src may be an important event in the genesis of human colon carcinoma.
结肠肿瘤为研究肿瘤进展提供了一个机会，因为大多数癌起源于腺瘤（息肉），而腺瘤又起源于正常上皮。腺瘤的恶性潜能随大小、组织学和发育异常程度而变化。小于2厘米、具有绒毛状结构和严重发育异常的息肉最有可能含有癌。先前的研究表明，结肠癌中pp60c-src的体外蛋白酪氨酸激酶活性显著高于相邻正常黏膜。在此我们报告，pp60c-src的蛋白激酶活性在结肠息肉中也升高。在恶性息肉以及大于2厘米、具有绒毛状结构和严重发育异常的良性息肉中活性最高。因此，pp60c-src的激活发生在发生癌症风险最大的良性息肉中。这些数据表明，原癌基因产物pp60c-src的激活可能是人类结肠癌发生中的一个重要事件。
