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http://ntur.lib.ntu.edu.tw/handle/246246/170424
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| 题名: | The Anti-Apoptotic Role of Interleukin-6 in Human Cervical Cancer Is Mediated by up-Regulation of Mcl-1 through a Pi3-K/Akt Pathway |
| 作者: | 魏凌鴻;郭明良;陳祈安;周佳宏;鄭文芳;張明誠;蘇振良;謝長堯
WEI, LIN-HUNG;KUO, MIN-LIANG;CHEN, CHI-AN;CHOU, CHIA-HUNG;CHENG, WEN-FANG;CHANG, MING-CHENG;SU, JEN-LIANG;HSIEH, CHANG-YAO |
| 贡献者: | 腫瘤醫學部 |
| 日期: | 2001 |
| 上传时间: | 2009-10-13T15:17:29Z |
| 摘要: | Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in human cervical cancer, though the mechanism remains elusive. This study demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly expressed in human cervical cancer tissues and cell lines, but not in normal cervix tissues. Upon IL-6 treatment, Mcl-1 , but not other Bcl-2 family members, was rapidly up- regulated peaking at 4-8 h in human cervical cancer C33A cells. Supporting this observation, using anti-IL-6 or anti- IL-6 receptor antibody to interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular level of Mcl-1 . This study hypothesizes that the expression of Mcl-1 in cervical cancer cells is regulated by IL-6. The matter of which signaling pathways transduced by IL-6 is responsible for the Mcl-1 up-regulation is further investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1 expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively abolished by treatment with PI 3-K inhibitors, LY294002. Additionally, overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6-induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading to the attenuation of their apoptosis-resistant activity. In conclusion, the data herein suggest that IL-6 regulated the mcl-1 expression via a PI 3 -K/Akt-dependent pathway that may facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold. |
| 關聯: | ONCOGENE v.20 n.41 pp.5799-5809 |
| 显示于类别: | [附設醫院腫瘤醫學部] 期刊論文
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