Differentially expressed genes associated with cis-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray

Differentially expressed genes associated with cis-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray
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DOI:
10.1002/hed.10204
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发表时间:
2003-03-01
影响因子:
2.9
通讯作者:
Fukuda, S
Fukuda, S
中科院分区:
医学2区
文献类型:
--
作者:
Higuchi, E;Oridata, N;Fukuda, S

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背景。癌细胞对顺式二胺二氯铂(cDDP)产生耐药性的机制尚不完全清楚。为了研究与cDDP耐药相关的分子标记,我们比较了一株对cDDP敏感的头颈部鳞状细胞癌(HNSCC)及其耐cDDP变异株的基因表达谱。采用荧光差异显示和cDNA微阵列分析方法,对人HNSCC细胞系KB及其抗cDDP变体(KB/cDDP)的基因谱进行了区分。这些结果经Northern blot分析证实。在KB/cDDP细胞中发现了1个糖蛋白激素α亚基上调基因和2个下调膜蛋白编码基因人叶酸受体和肿瘤相关抗原L6。我们的研究结果表明,抗cddp表型的发展伴随着基因表达的改变,包括糖蛋白激素和膜蛋白。这些基因产物可能成为新的cDDP抗性分子标记。(C) 2003 Wiley期刊有限公司
Background. The mechanism by which cancer cells become resistant to cis-Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant.Methods. Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis.Results. One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells.Conclusions. Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP. (C) 2003 Wiley Periodicals, Inc.