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

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 kno...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (31), p.12909-12914
Main Authors: Graveel, Carrie R, DeGroot, Jack D, Su, Yanli, Koeman, Julie, Dykema, Karl, Leung, Samuel, Snider, Jacqueline, Davies, Sherri R, Swiatek, Pamela J, Cottingham, Sandra, Watson, Mark A, Ellis, Matthew J, Sigler, Robert E, Furge, Kyle A, Vande Woude, George F
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - etiology
Adenocarcinoma - genetics
Animals
Basal cell carcinoma
Biological Sciences
Breast cancer
Breast Neoplasms - etiology
Breast Neoplasms - genetics
Breasts
Cancer
Correlation analysis
Female
Gene Amplification
Gene expression
Humans
Immunohistochemistry
Laboratory staining techniques
Mammary Neoplasms, Experimental - etiology
Mammary Neoplasms, Experimental - genetics
Mice
Mice, Inbred C57BL
Oncogenes
Proto-Oncogene Proteins c-met - genetics
Proto-Oncogene Proteins c-met - physiology
Receptor, ErbB-2 - analysis
Receptors, Progesterone - analysis
Rodents
Signal Transduction
Signatures
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0810403106