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Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer.


ABSTRACT: Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Met(mut)) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and ERBB2 expression, and expression of cytokeratin 5. With gene expression and tissue microarray analysis, we show that high MET expression in human breast cancers significantly correlated with estrogen receptor negative/ERBB2 negative tumors and with basal breast cancers. Few treatment options exist for breast cancers of the basal or trastuzumab-resistant ERBB2 subtypes. We conclude from these studies that MET may play a critical role in the development of the most aggressive breast cancers and may be a rational therapeutic target.

SUBMITTER: Graveel CR 

PROVIDER: S-EPMC2722304 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer.

Graveel Carrie R CR   DeGroot Jack D JD   Su Yanli Y   Koeman Julie J   Dykema Karl K   Leung Samuel S   Snider Jacqueline J   Davies Sherri R SR   Swiatek Pamela J PJ   Cottingham Sandra S   Watson Mark A MA   Ellis Matthew J MJ   Sigler Robert E RE   Furge Kyle A KA   Vande Woude George F GF  

Proceedings of the National Academy of Sciences of the United States of America 20090630 31


Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Met(mut)) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and ER  ...[more]

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