DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis
DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis
复制标题
DOI：
10.1038/sj.onc.1209802
复制
发表时间：
2007-01-01
期刊：
影响因子：
8
通讯作者：
Cheng, A-J
中科院分区：
文献类型：
--
作者：
Chen, Y-J;Chang, J. T.;Cheng, A-J
为了确定可能作为人类头颈癌(HNC)分子治疗标志物的基因，我们使用差异显示分析比较了HNC和组织病理学正常的上皮组织中的基因表达谱。通过逆转录-聚合酶链式反应和Western印迹分析，证实桥粒芯糖蛋白3(DSG3)在RNA和蛋白质水平均有差异表达。在56例鼻咽癌中，34例(61%)有DSG3过表达，其表达与T分期(P=0.009)、N分期(P=0.047)、总分期(P=0.011)、肿瘤深度(P=0.009)、淋巴结外扩散(P=0.044)等因素有关。与临床结果一致的是，通过RNA干扰(RNAi)抑制DSG3显著降低了三种HNC细胞系的细胞生长和克隆形成，降幅为57-21%。利用体外伤口愈合和Matrigel侵袭实验，我们发现在所测试的三种细胞系中，细胞的迁移和侵袭能力也被抑制了30%-48%。体内移植实验表明，DSG3-RNAi对BALB/C裸鼠的肿瘤生长有明显的抑制作用，持续2个月。综上所述，DSG3在HNC中高表达，其表达程度与肿瘤的临床病理特征有关。在细胞和动物体内的研究中，抑制DSG3显著抑制致癌潜力。这些发现表明，DSG3是开发HNC辅助治疗的潜在分子靶点。
To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer ( HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription - polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P=0.009), N stage (P = 0.047), overall stage (P = 0.011), tumor depth (P = 0.009) and extracapsular spread in lymph nodes (P = 0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57 - 21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30 - 48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.