【摘要】 鼻咽癌组织在染色体3p,9p,6q,11q,13 q和14q等区域存在较高的等位基因不平衡,表明这些区域存在与鼻咽癌相关的抑瘤基因。采用cDNA代表性差异分析等方法成功获得了候选的鼻咽癌易感/抑瘤基因,并进行了基因功能研究。发现:(1)Cx基因的表达增强是由于肿瘤细胞为突破细胞通讯功能的障碍,试图重建细胞间隙连接的一种表达变异;(2)BRD7基因是一个与细胞周期调控密切相关的核转录调控因子;(3)NAG7基因具有双重生物学功能——在抑制低侵袭能力的HNE1细胞增殖的同时,能够增加HNE1和6-10B细胞的侵袭潜能;(4)NGX6可以与Ezrin发生交互作用,参与鼻咽癌转移;(5)SPLUNC1基因的表达下调是鼻咽癌早期预警的分子诊断标志物。这些易感/抑瘤基因的功能基因组学研究为阐明鼻咽癌的发病机制打下了坚实的理论基础。更多还原

【Abstract】 There is obvious allele disequilibrium in nasopharyngeal carcinoma at chromosome 3p,9p,6q,11q,13q and 14q.Nasopharyngeal carcinoma(NPC) susceptibility/suppressor gene candidates were obained by molecular biology methods,such as cDNA representational difference ana-lysis.The functional research of NPC susceptibility/ suppressor gene candidates indicated:(1)The increased expression of Cx contributed to obstacles of gap junctional intercellular communication(GJIC),and resulted an aberration of GJIC;(2) BRD7,a transcript factor,was associated with cell cycle regulation;(3) NAG7,an estrogen receptor repressor,inhibited the invasive potential of human NPC cells by regulating ERα expression and the H-ras/p-c-Raf and JNK/AP-1/MMP1 signaling pathways;(4) NGX6,a metastasis-associated protein,can negative-regulate EGF/Ras/MAPK signaling transduction pathway,and interact with ezrin protein to inhibit invasion and metastasis of NPC cells;(5)SPLUNC1,a secreted protein,can inhibit the bacterium clone formation,and is an innate immune molecule.These data will lay an important foundation for the NPC mechanism.更多还原