Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype
Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype
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DOI：
10.1002/mc.20843
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发表时间：
2012-09-01
影响因子：
4.6
通讯作者：
Villanueva, Alberto
中科院分区：
文献类型：
--
作者：
Aytes, Alvaro;Mollevi, David G.;Villanueva, Alberto
染色体4p上的等位基因不平衡在许多不同的肿瘤类型中都有很大的报道。在结直肠癌中，4p15的杂合性缺失(LOH)与肿瘤的侵袭性和不良的患者预后相关，然而，到目前为止，该区域还没有发现任何靶基因。由于基质相互作用分子2(STIM2)位于4p15.2，已被认为是多形性胶质母细胞瘤中该区域的候选基因，本研究旨在探讨STIM2在结直肠癌中的作用。我们研究了一组移植的原发大肠肿瘤(n=20)和一组注释良好的结直肠癌系列肿瘤(n=140)中STIM2转录的表达水平。我们观察到，在63.5%的病例中，STIM2过表达与侵袭性较小的表型有关。体外和体内对结肠癌细胞株的功能研究表明，STIM2的过表达分别抑制了细胞的增殖和肿瘤的生长。我们的工作提供了几条证据表明，STIM2的过度表达是结直肠癌中一种常见的导致细胞生长抑制的特征，证明即使在没有体细胞遗传或表观遗传学改变的情况下，LOH的复发区域仍然应该被认为是存在与肿瘤发生相关的基因的标志。(C)2011年威利期刊公司。
Allelic imbalances at chromosome 4p have been largely documented in many different tumor types. In colorectal cancer, loss of heterozygosity (LOH) at 4p15 has been associated with tumor aggressiveness and poor patient outcome, however no target genes in the region have been identified to date. Since stromal interaction molecule 2 (STIM2) is located at 4p15.2 and has been proposed as a candidate gene for this region in glioblastoma multiforme, we aimed at investigating the role of STIM2 in colorectal cancer. We studied STIM2 transcript expression levels in a collection of xenografted primary colorectal tumors (n?=?20) and a well-annotated tumor series of colorectal cancer (n?=?140). We observed an overexpression of STIM2 in 63.5% of the cases that was associated with a less invasive phenotype. In vitro and in vivo functional studies with colon cancer cell lines revealed that overexpression of STIM2 reduced cell proliferation and tumor growth, respectively. Our work presents several lines of evidence indicating that STIM2 overexpression is a frequent trait in colorectal cancer that results in cell growth suppression, certifying that even in the absence of somatic genetic or epigenetic alterations, recurrent regions of LOH should still be considered a hallmark for the presence of relevant genes for tumorigenesis. (c) 2011 Wiley Periodicals, Inc.