文章基本信息

标题：Genetic determinants of neoplastic transformation by the retroviral oncogene v-erbB
本地全文：下载
作者：A Wells ; J M Bishop
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1988
卷号：85
期号：20
页码：7597-7601
DOI：10.1073/pnas.85.20.7597
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The retroviral oncogene v-erbB is a mutant version of the gene (c-erbB or ERBB1) that encodes the cell-surface epidermal growth factor receptor (EGFR). The mutations take three forms: (i) a large deletion that removes the entire ligand-binding domain of EGFR, (ii) smaller deletions that affect the carboxyl-terminal domain of EGFR, and (iii) point mutations that cause conservative substitutions of amino acids. Previous work has shown that, in the absence of the large deletion, ERBB1 cannot transform cells autonomously. Here we report that when the large deletion is present, no other mutation is required for ERBB1 to transform established rodent fibroblasts to a tumorigenic phenotype. In particular, there is no need for deletions affecting the carboxyl terminus of the gene product. It appears, therefore, that removal of the ligand-binding domain from the EGFR suffices to create a transforming protein. Deletions at the carboxyl terminus of the EGFR apparently play only a secondary role in transformation by affecting the host range and perhaps the potency of transformation; and there is as yet no evidence to implicate point mutations in the activation of ERBB1 to an oncogene. Our findings support the view that augmented activity of the EGFR can contribute to tumorigenesis.