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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Initiating oncogenic event determines gene-expression patterns of human breast cancer models
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Initiating oncogenic event determines gene-expression patterns of human breast cancer models

机译：启动致癌事件决定了人类乳腺癌模型的基因表达模式

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摘要

Molecular expression profiling of tumors initiated by transgenic overexpression of c-myc, c-neu, c-ha-ras, polyoma middle T antigen (PyMT) or simian virus 40 T/t antigen (T-ag) targeted to the mouse mammary gland have identified both common and oncogene-speclfic events associated with tumor formation and progression. The tumors shared great similarities in their gene-expression profiles as compared with the normal mammary gland with an induction of cell-cycle regulators, metabolic regulators, zinc finger proteins, and protein tyrosine phosphatases, along with the suppression of some protein tyrosine kinases. Selection and hierarchical clustering of the most variant genes, however, resulted in separating the mouse models into three groups with distinct oncogene-specific patterns of gene expression. Such an identification of targets specified by particular oncogenes may facilitate development of lesion-specific therapeutics and preclin-ical testing. Moreover, similarities in gene expression between human breast cancers and the mouse models have been identified, thus providing an important component for the validation of transgenic mammary cancer models.
机译：由针对小鼠乳腺的c-myc，c-neu，c-ha-ras，多瘤中期T抗原（PyMT）或猿猴病毒40 T / t抗原（T-ag）的转基因过表达引发的肿瘤分子表达谱已经确定了与肿瘤形成和进展相关的常见和致癌基因特异性事件。与正常乳腺相比，这些肿瘤在基因表达谱上有很大相似之处，它们诱导了细胞周期调节剂，代谢调节剂，锌指蛋白和蛋白酪氨酸磷酸酶，并且抑制了某些蛋白酪氨酸激酶。但是，对大多数变异基因的选择和层次聚类将小鼠模型分为具有基因表达的独特癌基因特异性模式的三组。对特定致癌基因指定的靶标的这种鉴定可以促进病变特异性治疗剂和临床前测试的发展。此外，已经确定了人类乳腺癌和小鼠模型之间基因表达的相似性，从而为验证转基因乳癌模型提供了重要的组成部分。

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