Attenuation of krüppel-like factor 4 facilitates carcinogenesis by inducing g1/s phase arrest in clear cell renal cell carcinoma.
Attenuation of krüppel-like factor 4 facilitates carcinogenesis by inducing g1/s phase arrest in clear cell renal cell carcinoma.
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DOI：
10.1371/journal.pone.0067758
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Song E;Ma X;Li H;Zhang P;Ni D;Chen W;Gao Y;Fan Y;Pang H;Shi T;Ding Q;Wang B;Zhang Y;Zhang X
Krüppel样因子4（KLF4）是一种在各种癌症类型中具有不同功能的转录因子;然而，KLF4在透明细胞肾细胞癌（ccRCC）癌变过程中的功能仍然未知。在这项研究中，我们首先使用一组手术切除的ccRCC标本和细胞系检测KLF4表达。结果表明，在ccRCC组织中KLF4的转录和翻译低于患者匹配的正常组织。此外，与正常肾近端小管上皮细胞系（HKC）相比，KLF4在5种ccRCC细胞系中在蛋白和mRNA水平上的表达显著下调。KLF4表达下调与肿瘤分期和肿瘤直径显著相关。启动子甲基化可能是其低表达的原因。此外，体外研究表明，KLF4过表达显著抑制人ccRCC细胞系786-O和ACHN的增殖。KLF4过表达可通过上调p21WAF1/CIP1表达和下调cyclin D1表达，使细胞周期阻滞于G1/S期，而KLF4敲低则相反。体内研究证实了KLF4的抗增殖作用。我们的研究结果表明，KLF4在抑制ccRCC的生长中具有重要作用。
Krüppel-like factor 4 (KLF4) is a transcription factor with diverse functions in various cancer types; however, the function of KLF4 in clear cell renal cell carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially examined KLF4 expression by using a cohort of surgically removed ccRCC specimens and cell lines. Results indicated that the transcription and translation of KLF4 were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore, the KLF4 expression was significantly downregulated in the five ccRCC cell lines at protein and mRNA levels compared with that in normal renal proximal tubular epithelial cell lines (HKC). KLF4 downregulation was significantly correlated with tumor stage and tumor diameter. Promoter hypermethylation may contribute to its low expression. In addition, in vitro studies indicated that the KLF4 overexpression significantly inhibited proliferation in human ccRCC cell lines 786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle progress at the G1/S phase transition by upregulating p21WAF1/CIP1 expression and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the opposite. In vivo studies confirmed the anti-proliferative effect of KLF4. Our results suggested that KLF4 had an important function in suppressing the growth of ccRCC.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
8
作者：
Foster, KW;Liu, ZL;Ruppert, JM
通讯作者：
Ruppert, JM
影响因子：
2.8
作者：
Barroca, H.;Castedo, S.;Mueller-Hoecker, J.
通讯作者：
Mueller-Hoecker, J.
影响因子：
3.7
作者：
Lin ZS;Chu HC;Yen YC;Lewis BC;Chen YW
通讯作者：
Chen YW
Krüpel 样因子 4 在正常体内平衡、癌症和干细胞中的作用。
影响因子：
3.7
作者：
Evans PM;Liu C
通讯作者：
Liu C