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[鼻咽癌易感/抑制基因的功能基因组学]

[Functional genomics of nasopharyngeal carcinoma susceptibility/suppressor gene].

作者信息

Li Xiao-Ling, Wu Ming-Hua, Li Gui-Yuan

机构信息

Cancer Research Institute, Central South University, Changsha 410078, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 Jul;33(7):553-8.

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 obtained 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 ERalpha 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.

摘要

在3号染色体的p臂、9号染色体的p臂、6号染色体的q臂、11号染色体的q臂、13号染色体的q臂和14号染色体的q臂上,鼻咽癌存在明显的等位基因不平衡。通过分子生物学方法,如cDNA代表性差异分析,获得了鼻咽癌(NPC)易感/抑制基因候选物。对NPC易感/抑制基因候选物的功能研究表明:(1)Cx表达增加导致细胞间隙连接通讯(GJIC)障碍,进而导致GJIC异常;(2)转录因子BRD7与细胞周期调控有关;(3)雌激素受体抑制因子NAG7通过调节ERα表达以及H-ras/p-c-Raf和JNK/AP-1/MMP1信号通路,抑制人鼻咽癌细胞的侵袭潜能;(4)转移相关蛋白NGX6可负向调节EGF/Ras/MAPK信号转导通路,并与埃兹蛋白相互作用,抑制NPC细胞的侵袭和转移;(5)分泌蛋白SPLUNC1可抑制细菌克隆形成,是一种天然免疫分子。这些数据将为鼻咽癌的发病机制奠定重要基础。

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