Initiating oncogenic event determines gene-expression patterns of human breast cancer models
Initiating oncogenic event determines gene-expression patterns of human breast cancer models
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DOI：
10.1073/pnas.102172399
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发表时间：
2002-05-14
影响因子：
11.1
通讯作者：
Green, JE
中科院分区：
文献类型：
--
作者：
Desai, KV;Xiao, N;Green, JE
由靶向小鼠乳腺的c-myc、c-neu、c-ha-ras、多瘤中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的分子表达谱已经鉴定了与肿瘤形成和进展相关的常见和癌基因特异性事件。与正常乳腺相比，肿瘤的基因表达谱具有很大的相似性，诱导细胞周期调节因子、代谢调节因子、锌指蛋白和蛋白酪氨酸磷酸酶，沿着一些蛋白酪氨酸激酶的抑制。然而，大多数变异基因的选择和层次聚类导致将小鼠模型分成三组，具有不同的癌基因特异性基因表达模式。这种由特定癌基因指定的靶点的鉴定可以促进病变特异性疗法和临床前测试的开发。此外，人类乳腺癌和小鼠模型之间的基因表达的相似性已被确定，从而为转基因乳腺癌模型的验证提供了重要组成部分。
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-specific 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 preclinical 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.