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Publication : Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer.

First Author  Ponzo MG Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  31 Pages  12903-8
PubMed ID  19617568 Mgi Jnum  J:151879
Mgi Id  MGI:4355475 Doi  10.1073/pnas.0810402106
Citation  Ponzo MG, et al. (2009) Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proc Natl Acad Sci U S A 106(31):12903-8
abstractText  Elevated MET receptor tyrosine kinase correlates with poor outcome in breast cancer, yet the reasons for this are poorly understood. We thus generated a transgenic mouse model targeting expression of an oncogenic Met receptor (Met(mt)) to the mammary epithelium. We show that Met(mt) induces mammary tumors with multiple phenotypes. These reflect tumor subtypes with gene expression and immunostaining profiles sharing similarities to human basal and luminal breast cancers. Within the basal subtype, Met(mt) induces tumors with signatures of WNT and epithelial to mesenchymal transition (EMT). Among human breast cancers, MET is primarily elevated in basal and ERBB2-positive subtypes with poor prognosis, and we show that MET, together with EMT marker, SNAIL, are highly predictive of poor prognosis in lymph node-negative patients. By generating a unique mouse model in which the Met receptor tyrosine kinase is expressed in the mammary epithelium, along with the examination of MET expression in human breast cancer, we have established a specific link between MET and basal breast cancer. This work identifies basal breast cancers and, additionally, poor-outcome breast cancers, as those that may benefit from anti-MET receptor therapies.
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