期刊文献+

硫酸乙酰肝素酶基因表达及其内切酶活性调控对肿瘤细胞浸润、转移作用的影响 被引量:4

Regulation of Heparanase Gene Expression and Endoglucuronidase Activity:Implication in Cell Invasion and Metastasis
在线阅读 下载PDF
导出
摘要 硫酸乙酰肝素酶是迄今为止在哺乳动物细胞中发现的唯一可以剪切胞外和细胞表面硫酸乙酰肝素多糖侧链的葡糖苷酸内切酶.在恶性肿瘤、炎症细胞以及胚胎组织等具有侵袭性组织中有较高的表达,肿瘤病人病灶部位的肝素酶mRNA表达量越高,病人存活期越短.在正常生理条件下,肝素酶基因及其表达蛋白的活性受到启动子甲基化、变化转录剪切、转录因子、蛋白质加工、pH环境以及免疫因子释放等多种内源因素的精确调控,以防止机体非正常恶性变化的发生.目前就有关乙酰肝素酶基因表达调控、酶活性的调控机制作详尽的专述. Heparanase is the only mammalian endo-β-D-glucuronidase known to cleave heparan sulfate (HS) components ofproteoglycans(PGs) at limited intra-chain sites. Heparanase release in response to an inflammatory stimulus or in relation to tumor metastasis alters the composition and structural integrity of extracellular matrix and basement membrane. The enzymatic degradation of HS by heparanase is, therefore, involved in range of biological phenomena, from pregnancy, morphogenesis and development to inflammation, vascularization, and cancer progression. In normal physiological processes, expression of the active enzyme is tightly regulated by promoter methylation, mRNA splicing, transcription factors, proteolytic processing and inflammatory cytokines. The recent findings about the strict regulation of heparanase product to yield the active enzyme are reviewed. from the expression of the gene to processing of the protein
作者 张怡 岑国欣
出处 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2005年第9期817-821,共5页 Progress In Biochemistry and Biophysics
基金 CRCG基金资助项目(10204997和10205634).~~
关键词 硫酸乙酰肝素酶 硫酸乙酰肝素蛋白聚糖 基因调控 内切酶活性 肿瘤细胞浸润 转移 heparanase, heparan sulfate proteoglycans, gene regulation, endoglucuronidase activity, cellinvasion, metastasis
  • 相关文献

参考文献29

  • 1Marchetti D, Denkins Y, Reiland J, et al. Brain-metastatic melanoma: a neurotrophic perspective. Pathol Oncol Res, 2003, 9(3): 147~ 158.
  • 2Parish C R, Freeman C, Hulett M D. Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta, 2001, 1471 (3):M99~108.
  • 3Vlodavsky I, Elkin M, Pappo O, et al. Mammalian heparanase as mediator of tumor metastasis and angiogenesis. Isr Med Assoc J,2000, (Suppl): 37~45.
  • 4Hulett M D, Freeman C, Hamdorf B J, et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis.Nat Med, 1999, 5 (7): 803~809.
  • 5Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase:gene cloning, expression and function in tumor progression and metastasis. Nat Med, 1999, 5 (7): 793~802.
  • 6Simizu S, Ishida K, Wierzba M K, et al. Expression ofheparanase in human tumor cell lines and human head and neck tumors. Cancer Lett, 2003,193 (1): 83~89.
  • 7Shteper P J, Zcharia E, Ashhab Y, et al. Role of promoter methylation in regulation of the mammalian heparanase gene.Oncogene, 2003, 22 (49): 7737~7749.
  • 8Dong J, Kukula A K, Toyoshima M, et al. Genomic organization and chromosome localization of the newly identified human heparanase gene. Gene, 2000, 253 (2):171 ~178.
  • 9Jiang P, Kumar A, Parrillo J E, et al. Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Spl in regulating HPR1 basal promoter activity. J Biol Chem, 2002, 277 (11): 8989~8998.
  • 10Lu W C, Liu Y N, Kang B B, et al. Trans-activation of heparanase promoter by ETS transcription factors. Oncogene, 2003, 22 (6):919~923.

同被引文献72

引证文献4

二级引证文献8

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部