SmgGDS is up-regulated in prostate carcinoma and promotes tumour phenotypes in prostate cancer cells.
SmgGDS is up-regulated in prostate carcinoma and promotes tumour phenotypes in prostate cancer cells.
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SmgGDS 在前列腺癌中上调并促进前列腺癌细胞的肿瘤表型。
DOI：
10.1002/path.2456
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Li,R
中科院分区：
文献类型：
--
作者：
Zhi,H;Yang,XJ;Kuhnmuench,J;Berg,T;Thill,R;Yang,H;See,WA;Becker,CG;Williams,CL;Li,R
SmgGDS是一种鸟嘌呤核苷酸交换因子，具有激活多个小gtpase的独特能力，暗示其参与癌症的发生和进展。本研究通过研究SmgGDS在前列腺良恶性组织中的表达，探讨SmgGDS在前列腺癌中的作用。我们还利用小干扰RNA （siRNA）检测了SmgGDS在三种前列腺癌细胞系中的功能。免疫组化分析显示SmgGDS水平在前列腺上皮内瘤变（PIN）、前列腺癌和转移性前列腺癌中升高。此外，SmgGDS的表达与环氧化酶- 2 （COX - 2）呈正相关，COX - 2是一种促进前列腺癌发展的蛋白。前列腺癌细胞中SmgGDS表达的减少抑制了增殖和迁移，与雄激素受体状态无关。这些影响伴随着COX‐2表达和NF‐κB活性的降低，NF‐κB是COX‐2的已知调节剂。综上所述，这些发现表明SmgGDS促进前列腺癌的发生和进展，可能与NF - κB依赖性的COX - 2上调有关。版权所有©2008英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
SmgGDS is a guanine nucleotide exchange factor with the unique ability to activate multiple small GTPases, implicating it in cancer development and progression. Here, we investigated the role of SmgGDS in prostate cancer by studying the expression of SmgGDS in benign and malignant prostatic tissues. We also probed SmgGDS function in three prostate carcinoma cell lines using small interfering RNA (siRNA). Immunohistochemical analysis revealed that SmgGDS levels were elevated in prostatic intraepithelial neoplasia (PIN), prostate carcinoma, and metastatic prostate carcinoma. In addition, expression of SmgGDS positively correlated with that of cyclooxygenase‐2 (COX‐2), a protein believed to promote the development of prostate carcinoma. Reduction of SmgGDS expression in prostate carcinoma cells inhibited proliferation and migration, irrespective of androgen receptor status. These effects were accompanied by a reduction in COX‐2 expression and in activity of NF‐κB, a known regulator of COX‐2. Taken together, these findings suggest that SmgGDS promotes the development and progression of prostate cancer, possibly associated with NF‐κB‐dependent up‐regulation of COX‐2. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.