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抵抗素在前列腺中的表达及其对前列腺癌细胞增殖的刺激作用。

Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation.

机构信息

Advanced Urogenital Disease Research Center, Chung-Ang University College of Medicine, Seoul, Korea.

出版信息

BJU Int. 2011 Jul;108(2 Pt 2):E77-83. doi: 10.1111/j.1464-410X.2010.09813.x. Epub 2010 Nov 2.

DOI:10.1111/j.1464-410X.2010.09813.x
PMID:21050358
Abstract

OBJECTIVES

To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. To identify the mechanisms underlying the activation of prostate cancer cells by resistin.

MATERIALS AND METHODS

Semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. Human full-length resistin gene (RETN) was transfected into the PC-3 cells using the pEGFP-N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC-3. Various concentrations of human recombinant protein resistin were added to the hormone-insensitive prostate cancer cell lines PC-3 and DU-145 for 48 h, and cell proliferation was assessed by a water-soluble tetrazolium salt assay.

RESULTS

Human prostate cancer cell lines PC-3 and DU-145 were found to express the human resistin mRNA. Resistin protein was strongly detected in high-grade prostate cancer tissue, whereas BPH or low-grade prostate cancer tissue revealed fainter expression of resistin. Cell proliferation was stimulated by both the full-length resistin gene overexpression and resistin treatment. Akt phosphorylation occurred after addition of resistin to PC-3 and DU-145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited PC-3 and DU-145 cell proliferation after resistin treatment.

CONCLUSIONS

Resistin is expressed in human prostate cancers. Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression.

摘要

目的

确定一种新型脂肪因子抵抗素是否能诱导前列腺癌细胞增殖。明确抵抗素激活前列腺癌细胞的机制。

材料与方法

采用半定量逆转录聚合酶链反应和免疫组织化学染色法检测前列腺上皮细胞抵抗素表达强度。将人全长抵抗素基因(RETN)转染到 PC-3 细胞中,使用 pEGFP-N1 载体来评估抵抗素在前列腺癌细胞系 PC-3 中的过表达效应。将不同浓度的人重组蛋白抵抗素添加到激素非依赖性前列腺癌细胞系 PC-3 和 DU-145 中 48 小时,通过水溶性四唑盐试验评估细胞增殖情况。

结果

人前列腺癌细胞系 PC-3 和 DU-145 表达人抵抗素 mRNA。抵抗素蛋白在高级别前列腺癌组织中强烈表达,而 BPH 或低级别前列腺癌组织则显示出较弱的抵抗素表达。全长抵抗素基因过表达和抵抗素处理均能刺激细胞增殖。在向 PC-3 和 DU-145 细胞添加抵抗素后,Akt 磷酸化发生。PI3K 药理学抑制剂 LY294002 显著抑制抵抗素处理后 PC-3 和 DU-145 细胞的增殖。

结论

抵抗素在人前列腺癌中表达。抵抗素通过 PI3K/Akt 信号通路诱导前列腺癌细胞增殖。抵抗素对前列腺癌细胞的增殖作用可能部分解释了前列腺癌的进展。

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