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Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive inva-sive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largelyunknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifenresistance; however, very little information is available regarding the genes whose loss-of-function alternation contrib-ute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells fromthe tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifenresistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, γ-glutamyltransferase-like activity 1,slit-robo RhoGTPase-activating protein, tetraspan NET-4, HSPC194, amiloride-sensitive epithelial sodium channel gene,and Notch2, were the eight mutated genes identified in different tamoxifen resistant clones, suggesting their requirementfor tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggeststhat multiple pathways can influence tamoxifen sensitivity in breast cancer cells.
The number of studies have revealed been over-activation of some signaling however, very little information is available regarding the genes whose loss-of-function alternation contrib-ute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells from the tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifenresistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, γ-glutamyltransferase-like activity 1, HSPC194, amiloride-sensitive epithelial sodium channel gene, and Notch2, were the eight mutated genes identified in di suggesting the requirement of tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggest that multiple pathways can influence tamoxifen sensitivity in breast cancer cells.