DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells.
DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells.
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DACH1抑制肾癌细胞cyclin D1表达、细胞增殖和肿瘤生长
DOI：
10.1186/s13045-014-0073-5
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发表时间：
2014-10-17
影响因子：
28.5
通讯作者：
Wu K
中科院分区：
文献类型：
--
作者：
Chu Q;Han N;Yuan X;Nie X;Wu H;Chen Y;Guo M;Yu S;Wu K
背景肾细胞癌（renal cell carcinoma，RCC）是一种具有多种生物学特性和独特分子标志的复杂肿瘤.针对驱动RCC启动和进展的分子的新靶向治疗在一些患者中取得了有希望的反应，但总有效率仍远未令人满意。腊肠犬（DACH1）网络是肾脏发育的关键信号通路，最近已被确定为几种癌症类型的肿瘤抑制因子。方法应用免疫组织化学方法检测DACH 1、PCNA和cyclin D1在人肾组织中的表达，并分析其与临床病理特征的关系，同时观察DACH 1在人肾癌细胞系中的异位表达和地西他滨处理对肾癌细胞增殖、凋亡和肿瘤生长的影响。通过Western blot、免疫沉淀和报告基因分析，探讨DACH 1的下游靶点和可能的分子机制。DACH1蛋白丰度与PCNA和cyclin D1表达、肿瘤分级和TNM分期呈负相关。肾透明细胞癌细胞中DACH 1功能的恢复抑制了体外细胞增殖、S期进展、克隆形成和体内肿瘤生长。结论DACH1是肾癌的一个新的分子标志物，与肾癌细胞的恶性行为有关。DACH1的重新激活可能是一种潜在的治疗策略。
BackgroundRenal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated.MethodsImmunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microaraays and correlation with clinic-pathological characteristics was analyzed.In vitroproliferation, apoptosis andin vivotumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays.ResultsExpression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibitedin vitrocellular proliferation, S phase progression, clone formation, andin vivotumor growth. In mechanism, DACH1 repressed cyclin D1 transcription through association with AP-1 protein.ConclusionOur results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy.
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影响因子：
3.7
作者：
Powe DG;Dhondalay GK;Lemetre C;Allen T;Habashy HO;Ellis IO;Rees R;Ball GR
通讯作者：
Ball GR
影响因子：
64.8
作者：
Li, X;Oghi, KA;Rosenfeld, MG
通讯作者：
Rosenfeld, MG
影响因子：
8.8
作者：
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影响因子：
6.6
作者：
Dalgin, Gul S.;Drever, Michele;Liou, Louis S.
通讯作者：
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影响因子：
28.5
作者：
Chen DL;Zeng ZL;Yang J;Ren C;Wang DS;Wu WJ;Xu RH
通讯作者：
Xu RH