Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts.

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作者：

Y Kokai，JN Myers，T Wada，VI Brown，CM Levea，JG Davis，K Dobashi，MI Greene

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摘要：

The protein product of the rodent neu oncogene, p185 neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c- erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c- neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless EGF is added to the cultures, and, even then, they are incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c- neu. During efforts to characterize the interaction of p185c- neu with EGFR further, we created cell lines that simultaneously overexpress both p185c- neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.

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关键词：

Animals Mice Fibroblasts Cell Line Cell Transformation, Neoplastic Receptor, Epidermal Growth Factor Receptor, erbB-2 Proto-Oncogene Proteins Transfection Gene Expression Regulation