Novel Strategies for the Treatment of Estrogen Receptor-Negative Breast Cancer
Annual summary rept. 4 Sep 2006-3 Mar 2009
BAYLOR COLL OF MEDICINE HOUSTON TX
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Previous gene expression profiling studies of breast cancer have focused on the entire genome to identify genes differentially expressed between estrogen receptor ER-positive and ER-negative cancers. Here we report a distinct kinase gene expression profile that identifies ER-negative breast tumors and subsets ER-negative breast tumors into 4 distinct subtypes. Furthermore, we show that this specific kinase profile is validated in breast cancer cell lines and independent sets of human tumors. Kinase expression knock-down studies show that many of these kinases are essential for the growth of ER-negative, but not ER-positive, breast cancer cell lines. Finally, survival analysis of patients with breast cancer shows that the S6 kinase pathway signature of ER-negative cancer confers an extremely poor prognosis, while patients whose tumors express high levels of immunomodulatory kinases have a significantly better prognosis. This study identifies a list of kinases that are prognostic and may serve as druggable targets for the treatment of ER-negative breast cancer.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research