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首页> 外文期刊>Molecular and Cellular Biology >Accelerated Mammary Tumor Development in Mutant Polyomavirus Middle T Transgenic Mice Expressing Elevated Levels of Either the Shc or Grb2 Adapter Protein
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Accelerated Mammary Tumor Development in Mutant Polyomavirus Middle T Transgenic Mice Expressing Elevated Levels of Either the Shc or Grb2 Adapter Protein

机译：表达shc或Grb2衔接蛋白的水平升高的突变多瘤病毒中T基因转基因小鼠中的乳腺肿瘤的发展。

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The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial development and tumorigenesis, we have generated transgenic mice which individually express the Grb2 and Shc proteins in the mammary epithelium. Although mammary epithelial cell-specific expression of Grb2 or Shc accelerated ductal morphogenesis, mammary tumors were rarely observed in these strains. To explore the potential role of these adapter proteins in mammary tumorigenesis, mice coexpressing either Shc or Grb2 and a mutant form of polyomavirus middle T (PyV mT) antigen in the mammary epithelium were generated. Coexpression of either Shc or Grb2 with the mutant PyV mT antigen resulted in a dramatic acceleration of mammary tumorigenesis compared to parental mutant PyV mT strain. The increased rate of tumor formation observed in these mice was correlated with activation of the epidermal growth factor receptor family and mitogen-activated protein kinase pathway. These observations suggest that elevated levels of the Grb2 or Shc adapter protein can accelerate mammary tumor progression by sensitizing the mammary epithelial cell to growth factor receptor signaling.
机译：Grb2和Shc衔接蛋白在激活的生长因子受体与几种细胞信号通路的偶联中起关键作用。为了评估这些分子在乳腺上皮发育和肿瘤发生中的作用，我们已经产生了在乳腺上皮中单独表达Grb2和Shc蛋白的转基因小鼠。尽管Grb2或Shc的乳腺上皮细胞特异性表达加速了导管形态发生，但在这些菌株中很少观察到乳腺肿瘤。为了探索这些衔接蛋白在乳腺肿瘤发生中的潜在作用，生成了在乳腺上皮中共表达Shc或Grb2和多瘤病毒中间T（PyV mT）抗原突变形式的小鼠。与亲本突变型PyV mT菌株相比，Shc或Grb2与突变型PyV mT抗原的共表达导致乳腺肿瘤发生的显着加速。在这些小鼠中观察到的肿瘤形成的增加速率与表皮生长因子受体家族的激活和有丝分裂原激活的蛋白激酶途径相关。这些观察结果表明，通过使乳腺上皮细胞对生长因子受体信号传导敏感，Grb2或Shc衔接子蛋白的水平升高可以加速乳腺肿瘤的进展。

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