结肠癌前病变中c-yes酪氨酸激酶活性升高。

Elevated c-yes tyrosine kinase activity in premalignant lesions of the colon.

作者信息

Peña S V, Melhem M F, Meisler A I, Cartwright C A

机构信息

Department of Medicine, Stanford University, California.

出版信息

Gastroenterology. 1995 Jan;108(1):117-24. doi: 10.1016/0016-5085(95)90015-2.

DOI:10.1016/0016-5085(95)90015-2

PMID:7806032

Abstract

BACKGROUND/AIMS: The cellular oncogene c-yes and its viral homologue v-yes (the transforming gene of Yamaguchi 73 and Esh avian sarcoma viruses) encode 62-kilodalton, cytoplasmic, membrane-associated, protein-tyrosine kinases. For the related Src kinase, a close correlation exists between elevated kinase activity and cell transformation. Previously, we observed elevated Yes activity in many human colon carcinomas. Colonic neoplasia provides an opportunity to study tumor progression because most carcinomas arise from adenomas, which in turn arise from normal epithelia. The malignant potential of adenomas varies with size, histology, and degree of dysplasia. Large adenomas (> or = 2 cm) with villous architecture and severe dysplasia are most likely to develop carcinoma.

METHODS

To determine whether Yes is activated in premalignant lesions of the colon, we measured its in vitro protein-tyrosine kinase activity in 21 colonic adenomas from 17 patients.

RESULTS

Activity of Yes in adenomas at greatest risk for cancer was significantly greater (12- or 14-fold as measured by enolase or autophosphorylation, respectively) than activity in adjacent normal mucosa. Moreover, villous structure, large size (> or = 2 cm), or severe dysplasia correlated with elevated Yes activity.

CONCLUSIONS

The activity of Yes is elevated in adenomas that are at greatest risk for developing cancer.

摘要

背景/目的：细胞癌基因c-yes及其病毒同源物v-yes（山口73和埃什禽肉瘤病毒的转化基因）编码62千道尔顿的胞质、膜相关蛋白酪氨酸激酶。对于相关的Src激酶，激酶活性升高与细胞转化之间存在密切关联。此前，我们观察到许多人类结肠癌中Yes活性升高。结肠肿瘤形成提供了一个研究肿瘤进展的机会，因为大多数癌起源于腺瘤，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。具有绒毛状结构和严重发育异常的大腺瘤（≥2厘米）最有可能发展为癌。