Peña S V, Melhem M F, Meisler A I, Cartwright C A
Department of Medicine, Stanford University, California.
Gastroenterology. 1995 Jan;108(1):117-24. doi: 10.1016/0016-5085(95)90015-2.
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.
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.
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.
The activity of Yes is elevated in adenomas that are at greatest risk for developing cancer.
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。
为了确定Yes在结肠癌前病变中是否被激活，我们检测了17例患者的21个结肠腺瘤的体外蛋白酪氨酸激酶活性。
癌症风险最高的腺瘤中Yes的活性（分别通过烯醇化酶或自身磷酸化测定，比相邻正常黏膜中的活性高12倍或14倍）显著更高。此外，绒毛状结构、大尺寸（≥2厘米）或严重发育异常与Yes活性升高相关。
在发生癌症风险最高的腺瘤中Yes的活性升高。
