Role of the MET Gene in Aggressive Breast Tumors Confirmed

Cancer researchers have identified a gene that when mutated plays a critical role in the development of aggressive estrogen receptor negative/ERBB2 (human epidermal growth factor receptor 2) negative tumors and with drug resistant basal breast cancers.

The MET gene is a proto-oncogene whose association with decreased survival in breast cancer has been recognized for many years. In the current study, investigators at Van Andel Research Institute (Grand Rapids, MI, USA) genetically engineered a line of mice that were "knocked in" and expressed elevated MET activity.

The investigators reported in the June 30, 2009, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) that these mice developed a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and ERBB2 expression, and expression of cytokeratin 5.

Results of experiments with gene expression and tissue microarray analysis showed that high MET expression in human breast cancers significantly correlated with estrogen receptor negative/ERBB2 negative tumors and with basal breast cancers.

These results support the premise that MET may play a critical role in the development of the most aggressive breast cancers and may be a rational therapeutic target. "MET has already been associated with decreased survival in breast cancer, but this study identifies its importance in specific types that can be distinguished at the molecular level," said senior author Dr. George Vande Woude, professor of medical oncology at Van Andel Research Institute.

Considering that many new inhibitors of MET are available for clinical trials, there is now a direct route for immediate application of these findings in the care of patients with this very aggressive form of breast cancer.

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Van Andel Research Institute