MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment
Pitroda SP et al. - In a trial to examine the effects of mucin 1 (MUC1) on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for breast cancer pts, it was shown that MUC1 regulates cholesterol and fatty acid metabolism, and activation of these pathways in estrogen receptor (ER)+ breast cancers predicts failure of tamoxifen treatment. Methods- An experimental model of MUC1-induced transformation was developed that has identified the activation of genes involved in cholesterol and fatty acid metabolism.
- A 38-gene set of experimentally derived MUC1-induced genes associated with lipid metabolism was applied to analysis of ER+ breast cancer pts treated with tamoxifen.
Results- Results obtained from 2 independent databases demonstrate that pts overexpressing MUC1 and lipid metabolic pathways are at significantly higher risk for death and recurrence/distant metastasis.
- These genes were not predictive in untreated pts.
- A positive correlation was found between expression of the 38-gene set and ER signaling pathway.
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