Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo
文献类型：期刊论文
| 作者 | Nelius, Thomas; Filleur, Stephanie; Yemelyanov, Alexander; Budunova, Irina; Shroff, E.; Mirochnik, Yelena; Aurora, Arin; Veliceasa, Dorina; Xiao, Wuhan; Wang, Zhou |
| 刊名 | INTERNATIONAL JOURNAL OF CANCER
 |
| 出版日期 | 2007-09-01 |
| 卷号 | 121期号:5页码:999-1008 |
| 关键词 | prostate cancer androgen receptor NF kappa B angiogenesis apoptosis |
| ISSN号 | 0020-7136 |
| 通讯作者 | Volpert, OV, Northwestern Univ, Feinberg Sch Med, Dept Urol, 303 E Chicago Ave, Chicago, IL 60611 USA |
| 中文摘要 | The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc. |
| 英文摘要 | The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Oncology |
| 类目[WOS] | Oncology |
| 研究领域[WOS] | Oncology |
| 关键词[WOS] | FACTOR-KAPPA-B ; HUMAN ENDOTHELIAL-CELLS ; CANCER CELLS ; INTRAEPITHELIAL NEOPLASIA ; CONSTITUTIVE ACTIVATION ; VENTRAL PROSTATE ; RESPONSE ELEMENT ; TYROSINE KINASE ; ATHYMIC MICE ; MOUSE MODELS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000248242500009 |
| 公开日期 | 2010-10-13 |
| 源URL | [http://ir.ihb.ac.cn/handle/152342/8490]  |
| 专题 | 水生生物研究所_中科院水生所知识产出（2009年前）_期刊论文 |
| 作者单位 | 1.Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA 2.Northwestern Univ, Feinberg Sch Med, Dept Pulm Med, Chicago, IL 60611 USA 3.Texas Tech Univ, Hlth Sci Ctr, Dept Urol, Lubbock, TX 79409 USA 4.Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA 5.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China 6.Univ Pittsburgh, Dept Urol, Pittsburgh, PA 15260 USA 7.Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA 15260 USA |
| 推荐引用方式 GB/T 7714 | Nelius, Thomas,Filleur, Stephanie,Yemelyanov, Alexander,et al. Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo[J]. INTERNATIONAL JOURNAL OF CANCER,2007,121(5):999-1008. |
| APA | Nelius, Thomas.,Filleur, Stephanie.,Yemelyanov, Alexander.,Budunova, Irina.,Shroff, E..,...&Volpert, Olga V..(2007).Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo.INTERNATIONAL JOURNAL OF CANCER,121(5),999-1008. |
| MLA | Nelius, Thomas,et al."Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo".INTERNATIONAL JOURNAL OF CANCER 121.5(2007):999-1008. |
入库方式： OAI收割
来源：水生生物研究所
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