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

Carrie R. Graveel, Jack D. DeGroot, Yanli Su, Julie Koeman, Karl Dykema, Samuel Leung, Jacqueline Snider, Sherri R. Davies, Pamela J. Swiatek, Sandra Cottingham, Mark A. Watson, Matthew J. Ellis, Robert E. Sigler, Kyle A. Furge, George F. Vande Woude

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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 (Metmut) 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.

Original languageEnglish
Pages (from-to)12909-12914
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number31
DOIs
StatePublished - Aug 4 2009

Keywords

  • ErbB2
  • Mouse model

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