Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling
文献类型：期刊论文
| 作者 | Zhang, Xi2; Mu, Xin3; Huang, Ou2; Xie, Zuoquan1 ; Jiang, Min2; Geng, Meiyu1; Shen, Kunwei2
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| 刊名 | PLOS ONE
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| 出版日期 | 2013-08-26 |
| 卷号 | 8期号:8 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0072053 |
| 文献子类 | Article |
| 英文摘要 | Background: Selective estrogen receptor modulators, such as tamoxifen, play a pivotal role in the treatment of luminal-type breast cancer. However, in clinical applications, nearly half of breast cancer patients are insensitive to tamoxifen, a small number of whom have early recurrence or disease progression when receiving tamoxifen. The underlying mechanism of this resistance has not been determined. ZNF703 is a novel oncogene in the 15% of breast cancers that harbor 8p12 amplifications. Therefore, the goal of our study was to explore the role of ZNF703 in tamoxifen resistance. Methodology/Principal Findings: We used immunohistochemistry techniques to examine ZNF703 expression in stage I-III primary breast cancer specimens and found a positive expression rate of 91.3%. All patients were divided into either high or low ZNF703 expression groups. We found that high ZNF703 expression mainly occurred in ER+ and PR+ breast cancers. Furthermore, 4-hydroxytamoxifen had different modes of action in breast cancer cell lines with high or low ZNF703 expression. ZNF703 overexpression in MCF-7 breast cancer cells activated the Akt/mTOR signaling pathway, downregulated ER alpha, and reduced the antitumor effect of tamoxifen. Low-dose tamoxifen did not suppress, but rather, stimulated the growth of cells overexpressing ZNF703. ZNF703 knockdown in MDA-MB-134 and HCC1500 luminal B-type breast cancer cell lines by siRNA significantly decreased survival rates when cells were treated with tamoxifen. Furthermore, targeting ZNF703 with a mTOR inhibitor increased the inhibitory effects of tamoxifen in ZNF703-overexpressing cells. Conclusion/Significance: Our study suggests that ZNF703 expression levels may predict tamoxifen sensitivity. Tamoxifen should be administered with caution to those patients bearing tumors with ZNF703 overexpression. However, large clinical trials and prospective clinical studies are needed to verify these results. |
| WOS关键词 | ESTROGEN-RECEPTOR STATUS ; GROWTH-FACTOR ; ENDOCRINE RESISTANCE ; THERAPEUTIC TARGET ; NEOADJUVANT TAMOXIFEN ; PROGESTERONE-RECEPTOR ; POSTMENOPAUSAL WOMEN ; NEGATIVE PHENOTYPE ; CROSS-TALK ; PATHWAY |
| 资助项目 | National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007] ; National Natural Science Foundation of China[81202087] ; National Natural Science Foundation of China[81202088] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000324228800040 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277497]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Geng, Meiyu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Comprehens Breast Hlth Ctr, Shanghai 200030, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Urol, Shanghai 200030, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Xi,Mu, Xin,Huang, Ou,et al. Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling[J]. PLOS ONE,2013,8(8). |
| APA | Zhang, Xi.,Mu, Xin.,Huang, Ou.,Xie, Zuoquan.,Jiang, Min.,...&Shen, Kunwei.(2013).Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling.PLOS ONE,8(8). |
| MLA | Zhang, Xi,et al."Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling".PLOS ONE 8.8(2013). |
入库方式： OAI收割
来源：上海药物研究所
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