Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer
文献类型：期刊论文
| 作者 | Chen, Guang; Yang, Na; Wang, Xiang; Zheng, Si-Yuan2; Chen, Yi1 ; Tong, Lin-Jiang; Li, Yi-Xue2; Meng, Ling-Hua; Ding, Jian
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| 刊名 | JOURNAL OF MOLECULAR MEDICINE-JMM
 |
| 出版日期 | 2010-09 |
| 卷号 | 88期号:9页码:941-952 |
| 关键词 | mTOR Biomarker p27 Rapamycin Rapalogs Cancer |
| ISSN号 | 0946-2716 |
| DOI | 10.1007/s00109-010-0635-0 |
| 文献子类 | Article |
| 英文摘要 | Rapamycin analogs temsirolimus and everolimus have been approved for the treatment of advanced renal cancer and are being tested in a wide spectrum of human tumors. However, objective response rates with rapalogs in clinical trials were modest and variable. Identification of biomarkers capable of predicting response to rapalogs is of increasing interest. We analyzed pairwise Pearson correlation coefficients (r) between rapalogs activity and gene expression profile for each NCI-60 cell line. p27 showed the highest positive correlation among 9,706 gene probes tested. At cellular levels, breast cancer MCF-7, T47D, and BT-474 cells, expressing high levels of p27, were sensitive to rapalogs, whereas the cells expressed low levels of p27, such as MDA-MB-231, MDA-MB-468, and MDA-MB-435 cells, exhibited resistance to rapalogs. Mechanistic study indicated that this correlation is likely determined by the basal level of p27 regardless of the phosphorylation or redistribution of p27 upon rapalogs treatment, which may provide a putative threshold to block G1/S transition. Consistently, down-regulation of p27 by siRNA conferred MCF-7 and BT-474 cells insensitive to rapalogs. Moreover, a significant positive correlation between p27 gene expression and rapamycin anti-tumor activity was also observed in mice bearing different human cancer cell xenografts. In conclusion, p27 expression level is positively correlated with the anticancer activity of rapalogs in vitro and in vivo. We propose p27 expression level may be also a candidate predictive biomarker for patient selection for rapalogsbased therapy, which requires clinical validation in a series of patients treated with rapalogs. |
| WOS关键词 | RECURRENT GLIOBLASTOMA-MULTIFORME ; RENAL-CELL CARCINOMA ; PHASE-II TRIAL ; BREAST-CANCER ; TEMSIROLIMUS CCI-779 ; INHIBITOR P27 ; DETERMINES SENSITIVITY ; ENHANCED SENSITIVITY ; RAD001 EVEROLIMUS ; MAMMALIAN TARGET |
| 资助项目 | National Science & Technology Major Project[2009ZX09301-001] ; National Science & Technology Major Project[2009ZX09102-025] ; National Natural Science Foundation of China[30721005] ; Science and Technology Commission of Shanghai Municipality Pujiang Talent Program[08PJ14114] ; Science and Technology Commission of Shanghai Municipality Pujiang Talent Program[07dz05906] ; Science and Technology Commission of Shanghai Municipality Pujiang Talent Program[074319113-2] |
| WOS研究方向 | Genetics & Heredity ; Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000280918800010 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278788]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Meng, Ling-Hua |
| 作者单位 | 1.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Liaoning, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Bioinformat Ctr, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Guang,Yang, Na,Wang, Xiang,et al. Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2010,88(9):941-952. |
| APA | Chen, Guang.,Yang, Na.,Wang, Xiang.,Zheng, Si-Yuan.,Chen, Yi.,...&Ding, Jian.(2010).Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer.JOURNAL OF MOLECULAR MEDICINE-JMM,88(9),941-952. |
| MLA | Chen, Guang,et al."Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer".JOURNAL OF MOLECULAR MEDICINE-JMM 88.9(2010):941-952. |
入库方式： OAI收割
来源：上海药物研究所
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