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Altered gene expression profiles of NIH3T3 cells regulated by human lung cancer associated gene CT120

机译:肺癌相关基因CT120调控NIH3T3细胞基因表达谱的改变

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CT120, a novel membrane-associated gene implicated in lung carcinogenesis, was previously identified from chromosome 17pl3.3 locus, a hot mutation spot involved in human malignancies. In the present study, we further determined that CI120 ectopic expression could promote cell proliferation activity of NIH3T3 cells using MTS assay, and monitored the downstream effects of CT120 in NIH3T3 cells with Atlas mouse cDNA expression arrays. Among 588 known genes, 133 genes were found to be upregulated or dowmegulated by CT120. Two major signaling pathways involved in cell proliferation, cell survival and anti-apoptosis were overexpressed and activated in response to CT120: One is the Raf/MEK/Eik signal cascades and the other is the P13K/Akt signal cascades,suggesting that CT120 might contribute, at least in part, to the constitutively activation of Eik and Akt in human lung caner cells. In addition, some tumor metastasis associated genes cathepsin B, cathepsin D, cathepsin L, MMP-2/TIMP-2 were also upregulated by CT120, upon which CT120 might be involved in tumor invasiveness and metastasis. In addition, CT120 might play an important role in tumor progression through modulating the expression of some candidate "Lung Tumor Progression"genes including B-Raf, Rab-2, BAX, BAG-1, YB-1, and Cdc42.
机译:CT120是一种与肺致癌有关的新型膜相关基因,先前已从染色体17p13.3位点(一个涉及人类恶性肿瘤的热点突变点)中鉴定出来。在本研究中,我们进一步确定使用MTS分析CI120异位表达可以促进NIH3T3细胞的细胞增殖活性,并使用Atlas小鼠cDNA表达阵列监测CT120在NIH3T3细胞中的下游作用。在588个已知基因中,有133个基因被CT120上调或下调。响应CT120,涉及细胞增殖,细胞存活和抗凋亡的两个主要信号通路被过表达和激活:一个是Raf / MEK / Eik信号级联,另一个是P13K / Akt信号级联,提示CT120可能参与至少部分是人类肺癌细胞中Eik和Akt的组成型活化。此外,CT120也上调了一些与肿瘤转移相关的组织蛋白酶B,组织蛋白酶D,组织蛋白酶L,MMP-2 / TIMP-2基因,CT120可能参与了肿瘤的侵袭和转移。另外,CT120可能通过调节某些候选“肺肿瘤进展”基因的表达而在肿瘤进展中发挥重要作用,这些基因包括B-Raf,Rab-2,BAX,BAG-1,YB-1和Cdc42。

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