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Current Opinion in Pharmacology, Vol. 12, No. 6. (December 2012), pp. 683-689, doi:10.1016/j.coph.2012.09.007 Key: citeulike:11451093
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The oncoprotein MUC-1 was shown to upregulate the transcription of genes encoding cholesterol and lipid metabolic enzymes and correlated with a resistance to Tamoxifen (Tam) despite the presence of estrogen receptor α in breast cancer tumors. The importance of this observation is supported by molecular studies on Tam suggesting two additional pharmacological targets involved in cholesterol metabolism. These observations demonstrate the potential importance of cholesterol and lipid metabolism in the pharmacology/therapeutic effects of Tam. . ⺠MUC1 upregulated the expression of the cholesterol metabolic pathway. ⺠Tam inhibits ACAT, cholesterol biosynthesis and ChEH activity and stimulates ROS production in tumor cells. ⺠Tumor initiating cells expressed MUC1 and are dysregulated for cholesterol metabolism. ⺠MUC1, ACAT, and ChEH are druggable targets for breast cancer treatment.
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