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A scheme showing the different mechanisms of tamoxifen resistance 1 Loss of ERО± expression and function lead to disappearance of the molecular target for tamoxifen 2 altered expression of coactivators or coregulators that play a critical role in ER mediated gene transcription, 3 ligand independent growth factor signaling cascades that activate kinases and ER phosphorylation, 4 altered availability of active tamoxifen metabolites regulated by drug metabolizing enzymes such as CYP2D6, 5 regulation of autophagy and or apoptosis, 6 ER negative cancer stem cells that differentiate over growth inhibition of ER positive cancer cells upon antiestrogen treatment, and 7 antioxidant protein mediated cell survival in which tamoxifen prevents repression of antioxidant proteins, such as Prx5 leading to cell survival and resistance to tamoxifen treatment buy cialis on line Conley had bit parts on 1960s series like Гў Green AcresГў and Гў The Beverly HillbilliesГў before he landed the role on CBSГў s Гў The WaltonsГў in 1972 that would last nearly a decade