胃癌组织中E26转录因子1表达与血管生成的相关性研究.DOCVIP

临床医学论文-胃癌组织中E26转录因子1表达与血管生成的相关性研究 ????????? 作者：丁印鲁 宫向前 李霞 傅勤烨 张建良 李兆亭 【摘要】目的：研究胃癌组织中E26转录因子1（Ets1）表达与血管生成的关系。方法：应用免疫组织化学方法（SP法）检测86例胃癌标本中Ets1的表达及微血管密度（MVD）；建立裸鼠胃癌皮下种植瘤模型，分别应用Ets1反义，正义寡核苷酸与PBS行瘤内注射，应用逆转录聚合酶链式反应检测瘤组织Ets1mRNA的变化，并检测瘤组织Ets1蛋白及微血管密度的差异。结果：胃癌组织中Ets1标记指数（LI）和MVD呈正相关（γ=0.495,P＜0.05）；经Ets1反义寡核苷酸治疗后，裸鼠瘤组织Ets1mRNA及Ets1蛋白表达降低，反义组MVD显著低于正义组与PBS组（10.4±3.1 VS 24.5±8.4,20.6±7.5,P＜0.01）。结论：胃癌组织中Ets1在促进血管生成中起重要作用。 ??? 【关键词】胃肿瘤?转录因子?寡脱氧核苷酸类，反义?新生血管化，病理性 ???? Correlation of Ets1 expression and angiogenesis in gastric cancer ????? 【ABSTRACT】Objective:To investigate the relationship of the expression of Ets1 and angiogenesis of gastric cancinoma.Methods:Expression of Ets1 and microvessel density(MVD)was detected immunohistochemically in paraffin imbedded specimens of 86 cases of gastric cancinoma.Human gastric carcinoma transplanted subcutaneously in nude mice model was constructed,and subquently the mice were devided into three groups:control group,sense oligoxydeonucleotide(sODN)group and antisense oligoxydeonucleotide(AsODN) group:After treatment respectively,changes of Ets1mRNA of transplanted tumor were detected by the reverse transcription polymerase chain reaction method(RTPCR),Ets1 protein and MVD was examined immunohistochemically.Results:A positive correlation was found between the expression of Ets1 and MVD in human gastric carcinoma tissues.Ets1 AsODN could underregulate the expression of Ets1mRNA and Ets1 protein.MVD of AsODN group was signicantly lower than control group and sODN group(P＜0.01).Conclusion:Ets1 may promote angiogenesis of gastric cancinoma. ??? 【KEY WORDS】Stomach neoplasms?Transcription factors?Oligoxydeonucleotide,antisense?Neovascularization,pathologic ??? 肿瘤的侵袭转移需要广泛的血管生成，而血管生成依赖于血管生成促进因子及抑制因子的调节。E26转录因子1（E26 transformationspecific1,Ets1）能够调节很多肿瘤基质降解与血管生成基因的转录，为此我们研究了胃癌组织中Ets1表达对血管生成的影响。 ??? 1? 材料与方法 ??? 1.1? 临床资料? 1996年7月~1999年12月山东大学齐鲁医院普通外科手术切除的86例胃癌标本，均经手术后病理证实。所有病人术前均未接受化疗、放疗或者其它针对肿瘤的治疗。男54例，女32例，年龄28~68岁，平均年龄（52.5±10.4）岁。 ??? 1.2? 寡核