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Notch、Myc与乳腺癌

Notch, Myc and breast cancer.

作者信息

Efstratiadis Argiris, Szabolcs Matthias, Klinakis Apostolos

机构信息

Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA.

出版信息

Cell Cycle. 2007 Feb 15;6(4):418-29. doi: 10.4161/cc.6.4.3838. Epub 2007 Feb 9.

Abstract

The involvement of Myc in the development of human breast cancer is known for quite some time, but an analogous role of Notch signaling is only now emerging from fragmented pieces of information. Recently, a Notch/Myc relationship in oncogenesis was revealed from a mouse model, in which mammary tumors are induced by the intracellular domain of Notch1 (N1(IC)). In fact, a combination of genetic and molecular data demonstrated that Myc is a direct transcriptional target of Notch1 participating as an indispensable downstream effector in N1(IC)-induced tumorigenic action. A medically-relevant correlative observation based on immunophenotyping was the coexpression of Notch1 and Myc in a significant fraction of human breast cancer specimens. A Notch1/Myc oncogenic association was also observed in T-cell acute lymphoblastic leukemia.

摘要

Myc参与人类乳腺癌的发展已为人所知有相当一段时间了,但Notch信号通路的类似作用只是现在才从零散的信息片段中显现出来。最近,从一个小鼠模型中揭示了Notch与Myc在肿瘤发生中的关系,在该模型中,Notch1的细胞内结构域(N1(IC))可诱导乳腺肿瘤。事实上,遗传和分子数据的结合表明,Myc是Notch1的直接转录靶点,作为N1(IC)诱导的致瘤作用中不可或缺的下游效应因子发挥作用。基于免疫表型分析的一项与医学相关的相关性观察是,在相当一部分人类乳腺癌标本中Notch1和Myc共表达。在T细胞急性淋巴细胞白血病中也观察到Notch1/Myc致癌关联。

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