c-Jun activation in acquired cystic kidney disease and renal cell carcinoma
c-Jun activation in acquired cystic kidney disease and renal cell carcinoma
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DOI：
10.1097/01.ju.0000164656.99251.77
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发表时间：
2005-08-01
影响因子：
6.6
通讯作者：
Murai, M
中科院分区：
文献类型：
--
作者：
Oya, M;Mikami, S;Murai, M
目的：激活蛋白1在细胞因子信号转导中起核心作用。激活蛋白-1由2个原癌基因家族组成，即Jun和Fos。其中c-Jun被认为在细胞周期进程和肿瘤转化中起作用。我们研究了c-Jun蛋白活化对肾细胞癌（RCC）病理参数的影响。材料与方法：采用免疫组化方法检测72例肾细胞癌（RCC）总c-Jun蛋白及磷酸化c-Jun蛋白的表达，其中10例为终末期肾脏获得性囊性肾病（ACKD）。结果：c-Jun在远端小管中表达，而在近端小管中无表达。ACKD的非典型增生细胞磷酸化c-Jun阳性。终末期肾脏发生的肾细胞癌为pT1，其中5例显示c-Jun激活增加。在62例肾脏功能正常的病例中，21例显示c-Jun激活程度增加。在局限性小细胞病例（pTla）中，55.5%（10 / 18）表现出增强激活，而这种增强激活仅在25%（11 / 44）的更晚期病例（pT1b或更高）中观察到。因此，c-Jun激活被认为与RCC的早期癌变有关。结论：本研究强调了c-Jun激活在早期RCC癌变中的作用。因此，慢性刺激细胞因子诱导c-Jun激活可能在ACKD和RCC中增生非典型细胞的异常增殖中起作用。
Purpose: Activator protein-1 has a central role in transducing cytokine signals. Activator protein-1 is composed of 2 proto-oncogene families, namely Jun and Fos. Of them c-Jun has been suggested to have a role in cell cycle progression and neoplastic transformation. We examined the impact of c-Jun protein activation on pathological parameters in renal cell carcinoma (RCC).Materials and Methods: The expression of total c-Jun protein and phosphorylated c-Jun protein was determined by immunohistochemistry in 72 patients with RCC, including 10 with tumor arising from acquired cystic kidney disease (ACKD) of end stage kidneys.Results: c-Jun expression was observed in the distal but not the proximal tubules. Atypical hyperplastic cells in ACKD were positive for phosphorylated c-Jun. RCC arising in end stage kidneys was pT1 and 5 of these cases showed increased c-Jun activation. Of 62 cases arising from normally functioning kidneys 21 showed an increased degree of c-Jun activation. In localized small cell cases (pTla) 55.5% (10 of 18) showed enhanced activation, whereas such enhanced activation was only observed in 25% (11 of 44) of more advanced cases (pT1b or greater). Therefore, c-Jun activation was considered to be related to the early carcinogenesis of RCC.Conclusions: This study emphasizes the role that c-Jun activation has in early RCC carcinogenesis. Thus, chronic stimulation of cytokines inducing c-Jun activation may have a role in the aberrant proliferation of hyperplastic atypical cells in ACKD and RCC.