1. MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ.
- Author
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Lü M, Ding K, Zhang G, Yin M, Yao G, Tian H, Lian J, Liu L, Liang M, Zhu T, and Sun F
- Subjects
- Animals, Antineoplastic Agents, Hormonal pharmacology, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cell Line, Tumor, Cell Survival drug effects, Cell Survival genetics, Estrogens pharmacology, Female, Gene Expression Regulation, Neoplastic drug effects, Gene Knockdown Techniques, Humans, MCF-7 Cells, Mice, Nude, Phosphoproteins metabolism, Progesterone pharmacology, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Receptors, Estrogen metabolism, Reverse Transcriptase Polymerase Chain Reaction, Xenograft Model Antitumor Assays methods, Breast Neoplasms drug therapy, Drug Resistance, Neoplasm genetics, MicroRNAs genetics, Phosphoproteins genetics, Receptors, Estrogen genetics, Tamoxifen pharmacology
- Abstract
Tamoxifen represents a major adjuvant therapy to those patients with estrogen receptor-alpha positive breast cancer. However, tamoxifen resistance occurs quite often, either de novo or acquired during treatment. To investigate the role of miR-320a in the development of resistance to tamoxifen, we established tamoxifen-resistant (TamR) models by continually exposing MCF-7 or T47D breast cancer cells to tamoxifen, and identified microRNA(miRNA)-320a as a down-regulated miRNA in tamoxifen resistant cells. Re-expression of miR-320a was sufficient to sensitize TamR cells to tamoxifen by targeting cAMP-regulated phosphoprotein (ARPP-19) and estrogen-related receptor gamma (ERRγ) as well as their downstream effectors, c-Myc and Cyclin D1. Furthermore, progesterone (P4) promoted the expression of miR-320a by repressing c-Myc expression, while estrogen (E2) exerted the opposite effect. These results suggest the potential therapeutic approach for tamoxifen-resistant breast cancer by restorating miR-320a expression or depleting ARPP-19/ERRγ expression.
- Published
- 2015
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