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学科主题临床医学
Nuclear Factor-KB-Mediated Transforming Growth Factor-beta-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy
Zhang, Qiang1,5; Helfand, Brian T.1; Jang, Thomas L.6; Zhu, Lihua J.7; Chen, Lin2; Yang, Ximing J.3,5; Kozlowski, James1,5; Smith, Norm1,5; Kundu, Shilajit D.6; Yang, Guangyu3,5; Raji, Adekunle A.3; Javonovic, Borko4,5; Pins, Michael3,5; Lindholm, Paul3,5; Guo, Yinglu8; Catalona, William J.1,5; Lee, Chung1,5
刊名CLINICAL CANCER RESEARCH
2009-05-15
DOI10.1158/1078-0432.CCR-08-1656
15期:10页:3557-3567
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者American Cancer Society (Illinois) ; American Cancer Society ; American Urological Association Foundation ; Department of Defense ; National Cancer Institute ; Illinois Department of Public Health ; American Cancer Society (Illinois) ; American Cancer Society ; American Urological Association Foundation ; Department of Defense ; National Cancer Institute ; Illinois Department of Public Health
研究领域[WOS]Oncology
关键词[WOS]EPITHELIAL-MESENCHYMAL TRANSITION ; RAS SIGNALING PATHWAYS ; CD8(+) T-CELLS ; NF-KAPPA-B ; TGF-BETA ; CANCER-CELLS ; METASTASIS ; PROGRESSION ; CARCINOGENESIS ; DEFINITION
英文摘要

Purpose: Transforming growth factor-beta (TGF-beta)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-beta and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-beta-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before.

Experimental Design: We analyzed TGF-beta-induced EMT using nuclear factor-KB (NF-KB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-beta signaling components and EMT-related factors were analyzed using specific antibodies.

Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-beta-induced EMT was mediated by NF-KB signaling. Blockade of NF-KB or TGF-beta signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-beta 1, vimentin, and NF-KB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients′ Gleason score.

Conclusions: The detection of NF-KB-mediated TGF-beta-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-beta signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.

语种英语
所属项目编号08-22 ; ACS-IRG 93-037-12 ; PC970410 ; PC001491 ; PC030038 ; CA90386 ; CA107186 ; CA114810 ; 83284034
资助者American Cancer Society (Illinois) ; American Cancer Society ; American Urological Association Foundation ; Department of Defense ; National Cancer Institute ; Illinois Department of Public Health ; American Cancer Society (Illinois) ; American Cancer Society ; American Urological Association Foundation ; Department of Defense ; National Cancer Institute ; Illinois Department of Public Health
WOS记录号WOS:000266282600035
Citation statistics
Cited Times:55[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58167
Collection北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Hosp 1, Inst Urol, Beijing 100871, Peoples R China
2.Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
3.Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA
4.Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA
5.Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA
6.Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA
7.Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
8.Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA
Recommended Citation
GB/T 7714
Zhang, Qiang,Helfand, Brian T.,Jang, Thomas L.,et al. Nuclear Factor-KB-Mediated Transforming Growth Factor-beta-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy[J]. CLINICAL CANCER RESEARCH,2009,15(10):3557-3567.
APA Zhang, Qiang.,Helfand, Brian T..,Jang, Thomas L..,Zhu, Lihua J..,Chen, Lin.,...&Lee, Chung.(2009).Nuclear Factor-KB-Mediated Transforming Growth Factor-beta-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy.CLINICAL CANCER RESEARCH,15(10),3557-3567.
MLA Zhang, Qiang,et al."Nuclear Factor-KB-Mediated Transforming Growth Factor-beta-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy".CLINICAL CANCER RESEARCH 15.10(2009):3557-3567.
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