Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray

Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray
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DOI:
10.1177/154405910208100805
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发表时间:
2002-08-01
影响因子:
7.6
通讯作者:
Knuutila, S
Knuutila, S
中科院分区:
医学1区
文献类型:
--
作者:
Heikinheimo, K;Jee, KJ;Knuutila, S

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成釉细胞瘤的分子和遗传特征仍知之甚少。我们利用cDNA微阵列分析了新鲜冷冻的成釉细胞瘤和人胎儿牙胚中的基因表达。34个基因在成釉细胞瘤中的表达水平有显著变化。11个基因过度表达超过3倍,23个基因表达下调至对照水平的0.4以下。癌基因FOS是过度表达最显著的基因(8到14倍),其次是肿瘤坏死因子受体1(TNFRSF1A)。音猬因子(SHH)、肿瘤坏死因子受体相关因子3(TRAF3)、rho GTP酶激活蛋白4(ARHGAP4)、结直肠癌缺失基因(DCC)、钙黏蛋白12和13(CDH12和CDH13)、畸胎瘤衍生生长因子1(TDGF1)以及转化生长因子β1(TGFB1)的基因在所有肿瘤中均表达下调。在选定的基因中,cDNA微阵列和实时逆转录聚合酶链反应之间的比较证实了相似的相对基因表达变化。基因表达谱确定了可能参与成釉细胞瘤起源的候选基因以及一些以前在人类牙齿发育方面未被确定的基因。
The molecular and genetic characteristics of ameloblastoma are still poorly understood. We analyzed gene expression in fresh-frozen ameloblastomas and human fetal tooth germs, using a cDNA microarray. Thirty-four genes exhibited significant changes in expression levels in the ameloblastoma. Eleven genes were overexpressed more than three-fold, and 23 genes were underexpressed to below 0.4 of the control level. The oncogene FOS was the most overexpressed gene (from eight- to 14-fold), followed by tumor-necrosis-factor-receptor 1 (TNFRSF1A). Genes for sonic hedgehog (SHH), TNF-receptor-associated-factor 3 (TRAF3), rhoGTP-ase-activating protein 4 (ARHGAP4), deleted in colorectal carcinoma (DCC), cadherins 12 and 13 (CDH12 and 13), teratocarcinoma-derived growth-factor-1. (TDGF1), and transforming growth-factor-beta1 (TGFB1) were underexpressed in all tumors. In selected genes, a comparison between cDNA microarray and real-time RT-PCR confirmed similar relative gene expression changes. The gene expression profile identifies candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development.