Relaxin promotes prostate cancer progression
Relaxin promotes prostate cancer progression
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DOI：
10.1158/1078-0432.ccr-06-2492
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发表时间：
2007-03-15
影响因子：
11.5
通讯作者：
Agoulnik, Alexander I.
中科院分区：
文献类型：
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作者：
Feng, Shu;Agoulnik, Irina U.;Agoulnik, Alexander I.
目的：为了理解松弛素肽在前列腺癌中的作用，我们分析了松弛素及其受体在人前列腺癌样品中的表达，松弛素信号传导对体外癌细胞表型的影响，以及血清松弛素浓度增加对体内癌症进展的影响。采用定量逆转录-PCR技术研究松弛素及其受体-富含亮氨酸重复序列的G蛋白偶联受体7（LGR 7）的表达（11个良性和44个癌症组织样品）和松弛素免疫组织化学，使用包含10个正常和69个癌症样品的组织微阵列。在体外分析松弛素处理和通过短干扰RNA在PC-3和LNCaP细胞中的促生长松弛素/LGR 7抑制的作用。在小鼠前列腺原位转基因腺癌（TRAMP）中评价转基因松弛素过表达[Tg（Rln 1）]对肿瘤生长和存活的影响。在10例正常组织的组织芯片中，8例上皮细胞低表达，而9例高级别前列腺上皮内瘤变病变中仅1例低表达（P = 0.005），65例癌中仅29例低表达（P = 0.047）。松弛素刺激增加细胞增殖，侵袭力和粘附在体外。通过短干扰RNA抑制松弛素/LGR 7使细胞侵袭性降低90%至95%，生长降低10%至25%，并使细胞凋亡增加0.6至2.2倍。Tg（Rln 1）TRAMP男性有较短的中位生存时间，与肿瘤细胞凋亡减少，与非Tg（R/n1）TRAMP animals.Conclusions：松弛素信号在前列腺癌的进展中起着重要作用。
Purpose: To understand the role of relaxin peptide in prostate cancer, we analyzed the expression of relaxin and its receptor in human prostate cancer samples, the effects of relaxin signaling on cancer cell phenotype in vitro, and the effects of increased serum relaxin concentrations on cancer progression in vivo.Experimental Design: The relaxin and its receptor leucine-rich repeat containing G protein coupled receptor 7 (LGR7) expression were studied by quantitative reverse transcription-PCR (11 benign and 44 cancer tissue samples) and by relaxin immunohistochemistry using tissue microarrays containing 10 normal and 69 cancer samples. The effects of relaxin treatment and enclogenous relaxin/LGR7 suppression via short interfering RNA in PC-3 and LNCaP cells were analyzed in vitro. The effect of transgenic relaxin overexpression [Tg(Rln1)] on cancer growth and survival was evaluated in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP).Results:The relaxin mRNA expression was significantly higher in recurrent prostate cancer samples. In tissue microarrays of the 10 normal tissues, 8 had low staining in epithelial cells, whereas only 1 of 9 high-grade prostatic intraepithelial neoplasia lesions had low expression (P = 0.005) and only 29 of 65 cancers had low expression (P = 0.047). Stimulation with relaxin increased cell proliferation, invasiveness, and adhesion in vitro. The suppression of relaxin/LGR7 via short interfering RNAs decreased cell invasiveness by 90% to 95% and growth by 10% to 25% and increased cell apoptosis 0.6 to 2.2 times. The Tg (Rln1) TRAMP males had shorter median survival time, associated with the decreased apoptosis of tumor cells, compared with non-Tg(R/n1) TRAMP animals.Conclusions: Relaxin signaling plays a role in prostate cancer progression.