國家衛生研究院 NHRI:Item 3990099045/8818
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    國家衛生研究院 NHRI > 癌症研究所 > 其他 > 期刊論文 >  Item 3990099045/8818


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    题名: The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma
    作者: Li, CF;Wu, WJ;Wu, WR;Liao, YJ;Chen, LR;Huang, CN;Li, CC;Li, WM;Huang, HY;Chen, YL;Liang, SS;Chow, NH;Shiue, YL
    贡献者: National Institute of Cancer Research
    摘要: In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/anchorage-independent cell growth via regulation of G2/M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the cAMP responsive element binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.
    日期: 2015-04-13
    關聯: Oncotarget. 2015 Apr 13;6(11):9220-9239.
    Link to: http://dx.doi.org/10.18632/oncotarget.3312
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000358774600056
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928714256
    显示于类别:[其他] 期刊論文

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