Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma.
Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma.
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DOI：
10.1016/j.molonc.2011.11.002
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发表时间：
2012-02
影响因子：
6.6
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Ding X;Zhang N;Cai Y;Li S;Zheng C;Jin Y;Yu T;Wang A;Zhou X
微管相关肿瘤抑制基因（MTUS 1，也称为线粒体肿瘤抑制基因）是最近发现的一种肿瘤抑制基因，与多种癌症类型有关。MTUS 1基因的表达导致5种已知的转录变体，并编码5种血管紧张素II AT 2受体相互作用蛋白（ATIP）亚型。在这项研究中，我们首次证实了MTUS 1/ATIP的下调是口腔舌鳞状细胞癌（OTSCC）和癌前病变（白斑）的常见事件。我们进一步证明了MTUS 1/ATIP的下调与分化不良和增殖增强（Ki 67增殖指数）相关。统计学分析表明，MTUS 1/ATIP的下调与总生存率降低相关。RT-PCR结果显示，MTUS 1基因在口腔舌上皮细胞中的主要亚型为ATIP 1、ATIP 3a和ATIP 3b。与匹配的正常组织相比，在OTSCC中观察到所有3种ATIP亚型的显著下调。体外功能研究表明，ATIP 1表达的恢复导致OTSCC细胞系G1期阻滞、凋亡和细胞增殖减少。这些ATIP 1诱导的细胞变化伴随着ERK 1/2磷酸化的减少和p53的上调。总之，这些数据表明MTUS 1在OTSCC的进展中起主要作用，并且可以作为OTSCC患者的生物标志物或治疗靶点。
Microtubule-associated tumor suppressor gene (MTUS1, also known as mitochondrial tumor suppressor) is a recently identified tumor suppressor gene that has been implicated in several cancer types. The expression of MTUS1 gene leads to 5 known transcript variants and codes for 5 isoforms of Angiotensin II AT2 receptor interacting protein (ATIP). In this study, we first confirmed that the down-regulation of MTUS1/ATIP was a frequent event in oral tongue squamous cell carcinoma (OTSCC) and the premalignant lesion (leukoplakia). We further demonstrated that the down-regulation of MTUS1/ATIP was correlated with poor differentiation and enhanced proliferation (Ki67 proliferation index). Statistical analysis suggests that the down-regulation of MTUS1/ATIP was associated with reduced overall survival. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in oral tongue epithelial cells. Significant down-regulations were observed for all 3 ATIP isoforms in OTSCC as compared to matching normal tissues. In vitro functional study showed that the restoration of ATIP1 expression led to G1 arrest, apoptosis and reduction of cell proliferation in OTSCC cell lines. These ATIP1-induced cellular changes were accompanied by reduced phosphorylation of ERK1/2 and up-regulation of p53. Taken together, these data suggest that MTUS1 plays major roles in the progression of OTSCC, and may serve as a biomarker or therapeutic target for patients with OTSCC.
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影响因子：
3
作者：
Yuen, APW;Lam, KY;Ho, CM
通讯作者：
Ho, CM
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1002/hed.2880150407
发表时间：
1993-07-01
影响因子：
2.9
作者：
LYDIATT, DD;ROBBINS, KT;WOLF, PF
通讯作者：
WOLF, PF
影响因子：
--
作者：
Zhou, XF;Jordan, RCK;Wong, DTW
通讯作者：
Wong, DTW
影响因子：
2.8
作者：
Louis, Simon N. S.;Chow, Laurie;Louis, William J.
通讯作者：
Louis, William J.