Enamel Matrix Derivative and TGF-Beta 1 Target Genes in Human Tongue Carcinoma Cells

M. Mauramo, Suvi‐Tuuli Vilén, T. Sorsa, T. Salo
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Abstract

Enamel matrix derivative (EMD) can enhance proliferation and migration of different oral cell lines, including malignant oral carcinoma cells, in vitro and in vivo. The composition of EMD is not known, but part of the effects have been postulated to be caused by transforming growth factor-beta-1 (TGF-beta 1). This study aimed to compare target genes of EMD and TGF-beta 1 on highly malignant oral carcinoma HSC-3 cells. Microarrays were used to examine differentially expressed genes in HSC-3 cells after 6h and 24h incubations with EMD (200 µg/ml) or TGF-beta 1 (10 ng/ml). Gene Ontology (GO) enrichment analysis of the regulated genes was also conducted. After 6h and 24h of EMD treatments 42 and 12 genes, respectively, were statistically significantly (P<0.05) up- or down-regulated. However, as many as 393 and 346 genes were statistically significantly (P<0.05) up- or down-regulated by TGF-beta 1. Among the most up-regulated genes by both of the study reagents were MMP-9 and -10. The expression of MMP-10 by EMD treated carcinoma cells was also verified in protein level. In conclusion, TGF-beta 1 regulates more and mostly different genes compared with EMD, but both regulate the expression of matrix metalloproteinase genes in oral carcinoma cells.
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人舌癌细胞中的釉基质衍生物和TGF-β1靶基因
釉质基质衍生物(EMD)可以在体内外增强不同口腔细胞系的增殖和迁移,包括恶性口腔癌细胞。EMD的成分尚不清楚,但部分作用被认为是由转化生长因子-β-1(TGFβ1)引起的。本研究旨在比较EMD和TGFβ-1在高度恶性口腔癌HSC-3细胞上的靶基因。使用微阵列检测用EMD(200µg/ml)或TGF-β1(10ng/ml)孵育6小时和24小时后HSC-3细胞中差异表达的基因。还对受调控基因进行了基因本体论(GO)富集分析。EMD处理6小时和24小时后,42个和12个基因分别上调或下调,具有统计学意义(P<0.05)。然而,多达393个和346个基因被TGF-β1上调或下调,具有统计学意义(P<0.05)。在这两种研究试剂调控的基因中,MMP-9和-10是最多的。EMD处理的癌细胞在蛋白质水平上也证实了MMP-10的表达。总之,与EMD相比,TGF-β1调节更多且大多数不同的基因,但两者都调节口腔癌细胞中基质金属蛋白酶基因的表达。
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