論文 - 詳細
| RRC ID | 38420 |
|---|---|
| 著者 | Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y. |
| タイトル | Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:To determine the relationship between resistance to chemotherapy and microRNA (miRNA) expression in esophageal cancer, we focused on miRNAs known to be associated with maintenance of stem cell function. EXPERIMENTAL DESIGN:Using 98 formalin-fixed, paraffin-embedded samples obtained from patients with esophageal cancer who had received preoperative chemotherapy followed by surgery, we measured expression levels of several miRNAs that are considered to be involved in the regulation of stem cell function (e.g., let-7a, let-7g, miR-21, miR-134, miR-145, miR-155, miR-200c, miR-203, and miR-296) by real-time reverse transcriptase PCR. Then, we examined the relationship between miRNA expression and prognosis or response to chemotherapy. To investigate the mechanism of miRNA-induced chemoresistance, in vitro assays were carried out using esophageal cancer cells. RESULTS:Analyses of the 9 miRNAs expression showed that overexpression of miR-200c (P = 0.037), underexpression of miR-145 (P = 0.023), and overexpression of miR-21 (P = 0.048) correlated significantly with shortened overall duration of survival. In particular, miR-200c expression correlated significantly with response to chemotherapy (P = 0.009 for clinical response; P = 0.007 for pathologic response). In vitro assay showed significantly increased miR-200c expression in cisplatin-resistant cells compared with their parent cells (∼1.7-fold). In anti-miR-200c-transfected cells, chemosensitivity to cisplatin and apoptosis after exposure to cisplatin was found to increase as compared with the negative control. Western blotting showed that knockdown of miR-200c expression was associated with increased expression of PPP2R1B, a subunit of protein phosphatase 2A, which resulted in reduced expression of phospho-Akt. CONCLUSIONS:Results of this study emphasized the involvement of miR-200c in resistance to chemotherapy among esophageal cancers and that this effect was mediated through the Akt pathway. |
| 巻・号 | 17(9) |
| ページ | 3029-38 |
| 公開日 | 2011-5-1 |
| DOI | 10.1158/1078-0432.CCR-10-2532 |
| PII | 1078-0432.CCR-10-2532 |
| PMID | 21248297 |
| MeSH | Aged Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use Carcinoma, Squamous Cell / diagnosis Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / surgery Cell Line, Tumor Cisplatin / pharmacology Cisplatin / therapeutic use Drug Resistance, Neoplasm / genetics* Enzyme Activation / genetics Enzyme Activation / physiology Esophageal Neoplasms / diagnosis Esophageal Neoplasms / drug therapy Esophageal Neoplasms / genetics* Esophageal Neoplasms / surgery Female Gene Expression Regulation, Neoplastic / physiology Humans Male MicroRNAs / genetics* MicroRNAs / physiology Middle Aged Oncogene Protein v-akt / metabolism* Oncogene Protein v-akt / physiology Prognosis Signal Transduction / genetics Signal Transduction / physiology Up-Regulation / genetics |
| IF | 10.107 |
| 引用数 | 168 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |