Identification of eight genes that are potentially involved in tamoxifen sensitivity in breast cancer cells.
Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive invasive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largely unknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifen resistance; however, very little information is available regarding the genes whose loss-of-function alternation contribute 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 tamoxifen resistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, g-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 requirement for tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggests that multiple pathways can influence tamoxifen sensitivity in breast cancer cells.
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tyler
T
Zarubin
Qing
Q
Jing
Liguo
L
New
Jiahuai
J
Han
D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics; D052138:Genes, Neoplasm; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000235:genetics
D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D012177:Retinol-Binding Proteins; D015222:Sodium Channels; D013629:Tamoxifen; D005723:gamma-Glutamyltransferase