Furuya Mitsuko, Nishiyama Mariko, Kimura Sadao, Suyama Takahito, Naya Yukio, Ito Haruo, Nikaido Takashi, Ishikura Hiroshi
Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
J Pathol. 2004 May;203(1):551-8. doi: 10.1002/path.1543.
The gene expression profiles of tumour and normal vasculature are distinctively different. The altered expression of various angiogenesis-related genes in tumour-derived endothelial cells has been investigated intensively, but there may be as yet unidentified molecules that regulate tumour angiogenesis. In the present study, the distinctive expression of regulator of G protein signalling protein 5 (RGS5) in tumour vessels in human renal cell carcinoma (RCC) has been clarified. RGS5 is a member of the RGS superfamily and acts as a negative regulator of heterotrimeric G protein-mediated signalling through G protein-coupled receptors (GPCRs). RT-PCR showed strong expression of RGS5 in all RCCs examined, but expression was very weak or undetectable in normal kidneys. By real-time RT-PCR, the ratio of RGS5 mRNA in RCC to that in normal kidney was 6.6 : 1 (p = 0.0012). In situ hybridization showed strong expression of RGS5 in vessels within tumour cell nests. It was expressed neither in tumour cells nor in normal renal capillaries. Immunohistochemical staining using serial sections for endothelial cell markers (CD31 and CD34) and smooth muscle cell markers (alpha-SMA and desmin), as well as fluorescence double staining, strongly suggested that tumour endothelial cells were the main location of RGS5 in RCC. These findings suggest that RGS5 may be involved in G protein-mediated signalling in tumour vessels in human RCC.
肿瘤血管和正常血管的基因表达谱存在显著差异。人们对肿瘤来源的内皮细胞中各种血管生成相关基因的表达改变进行了深入研究，但可能仍存在尚未被识别的调节肿瘤血管生成的分子。在本研究中，已阐明了G蛋白信号调节蛋白5（RGS5）在人肾细胞癌（RCC）肿瘤血管中的独特表达。RGS5是RGS超家族的成员，通过G蛋白偶联受体（GPCRs）作为异三聚体G蛋白介导信号的负调节因子。逆转录聚合酶链反应（RT-PCR）显示，在所检测的所有肾细胞癌中RGS5均有强表达，但在正常肾脏中表达非常弱或无法检测到。通过实时RT-PCR，肾细胞癌中RGS5 mRNA与正常肾脏中RGS5 mRNA的比值为6.6 : 1（p = 0.0012）。原位杂交显示RGS5在肿瘤细胞巢内的血管中有强表达。它在肿瘤细胞和正常肾毛细血管中均不表达。使用内皮细胞标志物（CD31和CD34）和平滑肌细胞标志物（α-平滑肌肌动蛋白和结蛋白）的连续切片进行免疫组织化学染色以及荧光双重染色，强烈提示肿瘤内皮细胞是肾细胞癌中RGS5的主要定位部位。这些发现表明，RGS5可能参与人肾细胞癌肿瘤血管中G蛋白介导的信号传导。
