摘要
信号转导子与转录活化子3(STAT3)是一个具有信号转导和转录调控双重功能的转录因子,有文献报道STAT3在乳腺癌中的表达显著升高,并能促进乳腺癌的转移。为了深入探索STAT3在肿瘤发生发展中的作用和影响乳腺癌转移的分子机制,采用RNA干扰技术在小鼠乳腺癌细胞株4T1中沉默STAT3的表达。MTT实验结果显示STAT3沉默对4T1细胞的增殖能力没有影响;细胞迁移实验结果表明STAT3表达被沉默后4T1细胞的迁移能力明显被抑制;定量PCR结果显示,STAT3基因沉默后4T1细胞中VEGF和IL-6的mRNA水平下降,E-cadherin表达上升,mosin表达下降;信号通路检测显示STAT3基因表达沉默后MAPK的活化明显降低。研究表明STAT3在小鼠乳腺癌细胞的迁移过程中发挥重要作用,为以STAT3基因为靶向的治疗提供了一定的实验依据。
STAT3(signal transducer and activator of transcription 3)is a dual functional transcription factor with functions as signal transduction and transcription regulation.There are reports that the expression of STAT3 in breast cancer is significantly higher and STAT3 can facilitate breast cancer metastasis.To clarify the definite effect and molecular mechanism of STAT3's involvement in breast cancer metastasis,STAT3 was silenced by RNAi in the murine highly metastatic 4T1 cells.The silencing of STAT3 didn't affect the proliferation rate of breast cancer 4T1 cells in MTT assay.However,the migration activity of STAT3 knockdown cells was strongly reduced in Transwell assay.The real-time quantitative PCR results indicated that STAT3 silencing significantly suppressed the expression of VEGF,IL-6 and mosin,while increased E-cadherin expression.Western blot assay showed that phosphorylation level of MAPK was reduced in STAT3 knockdown cells.The results demonstrate that STAT3 plays an important role in breast cancer metastasis and provide experimental evidences in therapy with STAT3 as a target.
出处
《中国生物工程杂志》
CAS
CSCD
北大核心
2010年第6期1-7,共7页
China Biotechnology
基金
国家"973"计划资助项目(2003CB716402)