Kruppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression
Kruppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression
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DOI：
10.1002/ijc.24538
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发表时间：
2009-10-15
影响因子：
6.4
通讯作者：
Shibata, Tatsuhiro
中科院分区：
文献类型：
--
作者：
Nakamura, Yu;Migita, Toshiro;Shibata, Tatsuhiro
胃癌是日本第二常见的恶性肿瘤，其低分化形式是一种致命的疾病。为了确定新的候选癌基因有助于其发生，我们研究了50个原发性低分化胃癌的拷贝数改变，使用基于阵列的比较基因组杂交（阵列CGH）。发现了许多遗传变化，包括13 q22基因座的新扩增。几个基因位于这个位点，和选择性敲低的一个Kruppel样因子12（KLF 12）诱导显着的生长停滞在HGC 27胃癌细胞系。基因芯片分析也表明，与细胞增殖相关的基因主要是由KLF 12敲低改变。为了探讨KLF 12的致癌功能，我们将人KLF 12全长cDNA导入NIH 3 T3和AZ-521细胞系，发现过表达显著增强了它们的侵袭能力。在临床标本中，28例胃癌组织中有11例（39%）KLF 12 mRNA表达高于正常胃粘膜。临床病理分析进一步证实KLF 12 mRNA水平与肿瘤大小显著相关（p = 0.038）。这些数据表明，KLF 12基因在低分化胃癌的进展中起着重要作用，是一个潜在的治疗措施的目标。(C)2009年UICC
Gastric cancer is the second common malignant neoplasia in,Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Kruppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures. (C) 2009 UICC