Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in renal cell carcinoma by hypermethylation.
Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in renal cell carcinoma by hypermethylation.
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DOI：
10.3892/ijo.2014.2314
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发表时间：
2014-05
影响因子：
5.2
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Lin J;Deng Z;Tanikawa C;Shuin T;Miki T;Matsuda K;Nakamura Y
为了确定参与肾癌发生的基因，我们使用由27，648个cDNA或EST组成的微阵列分析了肾细胞癌（RCC）的表达谱，发现小的热休克蛋白HSPB 7在RCC中显著且普遍下调。随后的定量PCR（qPCR）和免疫组化（IHC）分析证实了RCC组织和癌细胞系中HSPB 7在转录和蛋白水平上的下调。HSPB 7基因组测序结果显示，肾细胞癌细胞中HSPB 7基因部分片段发生了DNA甲基化，5-Aza-dC处理后HSPB 7的表达明显恢复。在5个RCC细胞系中异位导入HSPB 7显著抑制癌细胞生长。有趣的是，我们发现HSPB 7的表达可以被p53以剂量依赖的方式诱导，表明该基因在p53通路中起作用。我们的研究结果表明，HSBP 7可能是一个受p53调控的抑癌基因，其过甲基化下调可能在肾癌发生中起关键作用。
In order to identify genes involved in renal carcinogenesis, we analyzed the expression profile of renal cell carcinomas (RCCs) using microarrays consisting of 27,648 cDNA or ESTs, and found a small heat shock protein, HSPB7, to be significantly and commonly downregulated in RCC. Subsequent quantitative PCR (qPCR) and immunohistochemical (IHC) analyses confirmed the downregulation of HSPB7 in RCC tissues and cancer cell lines in both transcriptional and protein levels. Bisulfite sequencing of a genomic region of HSPB7 detected DNA hypermethylation of some segments of HSPB7 in RCC cells and concordantly 5-aza-2′-deoxycytidine (5-Aza-dC) treatment of cancer cells restored HSPB7 expression significantly. Ectopic introduction of HSPB7 in five RCC cell lines remarkably suppressed cancer cell growth. Interestingly, we found that HSPB7 expression could be induced by p53 in a dose-dependent manner, indicating that this gene functions in the p53 pathway. Our results imply that HSBP7 is likely to be a tumor suppressor gene regulated by p53 and its downregulation by hypermethylation may play a critical role in renal carcinogenesis.
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影响因子：
2.7
作者：
Rosenfeld, Gabriel E.;Mercer, Emily J.;Mason, Christopher E.;Evans, Todd
通讯作者：
Evans, Todd
影响因子：
4.5
作者：
Stark K;Esslinger UB;Reinhard W;Petrov G;Winkler T;Komajda M;Isnard R;Charron P;Villard E;Cambien F;Tiret L;Aumont MC;Dubourg O;Trochu JN;Fauchier L;Degroote P;Richter A;Maisch B;Wichter T;Zollbrecht C;Grassl M;Schunkert H;Linsel-Nitschke P;Erdmann J;Baumert J;Illig T;Klopp N;Wichmann HE;Meisinger C;Koenig W;Lichtner P;Meitinger T;Schillert A;König IR;Hetzer R;Heid IM;Regitz-Zagrosek V;Hengstenberg C
通讯作者：
Hengstenberg C
影响因子：
64.5
作者：
Oda, K;Arakawa, H;Taya, Y
通讯作者：
Taya, Y
影响因子：
8
作者：
Huang, Z.;Cheng, Y.;Lung, M. L.
通讯作者：
Lung, M. L.
影响因子：
21.3
作者：
Tanikawa, C;Matsuda, K;Arakawa, H
通讯作者：
Arakawa, H