中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2011年
5期
358-362
,共5页
吴晓慧%王顺祥%杨永江%李建坤%徐卓%唐瑞峰
吳曉慧%王順祥%楊永江%李建坤%徐卓%唐瑞峰
오효혜%왕순상%양영강%리건곤%서탁%당서봉
肝肿瘤%Raf激酶抑制蛋白%肿瘤转移%p65%磷酸化细胞外调节蛋白激酶
肝腫瘤%Raf激酶抑製蛋白%腫瘤轉移%p65%燐痠化細胞外調節蛋白激酶
간종류%Raf격매억제단백%종류전이%p65%린산화세포외조절단백격매
Liver neoplasms%Raf kinase inhibitor protein%Neoplasm metastasis%p65%pERK
目的 探讨Raf激酶抑制蛋白(RKIP)与肝细胞癌(HCC)侵袭转移的关系.方法 采用逆转录聚合酶链反应(RT-PCR)方法检测HCC、癌旁组织及正常肝组织中RKIP mRNA的表达,采用免疫组织化学和Western blot法检测不同肝组织中RKIP、p65和磷酸化细胞外调节蛋白激酶(pERK)蛋白的表达,分析RKIP表达与HCC临床病理学特征的关系及其与p65和pERK表达的相关性.结果 HCC、癌旁组织和正常肝组织中RKIP mRNA的表达量分别为1.357±0.569、1.512±0.623和1.550±0.426,组问差异无统计学意义(P>0.05).HCC、癌旁组织和正常肝组织中,RKIP蛋白的表达量分别为0.579±0.380、1.178±0.659和1.115±0.442,p65蛋白的表达量分别为0.830±0.376、0.630±0.337和0.466±0.345,pERK蛋白的表达量分别为1.023±0.478、0.605±0.367和0.461±0.293.免疫组织化学结果显示,HCC、癌旁组织和正常肝组织中,RKIP的阳性表达率分别为22.2%、86.0%和93.8%,p65的阳性表达率分别为73.6%、56.0%和37.5%;pERK的阳性表达率为65.3%、38.0%和31.3%.RKIP蛋白在HCC组织中的表达显著低于癌旁组织及正常肝组织,而p65和pERK在HCC组织中的表达均显著高于癌旁组织及正常肝组织(均P<0.05).RKIP蛋白表达水平与HCC分化程度和有尤门静脉或胆管癌柃情况有关(P<0.05),p65蛋白表达水平与HCC分化程度和有无门静脉或胆管癌栓有关,pERK蛋白表达水平与HCC分化程度、有无门静脉或胆管癌栓和肝内或淋巴结转移情况有关(均P<0.05).HCC组织中RKIP的表达与pERK的表达相关(P=0.04),但与p65的表达无关(P=0.143).结论 RKIP表达的减少或缺失、p65和pERK的高表达与HCC的发生发展、侵袭转移密切相关.RKIP可能通过下调pERK的表达抑制HCC的侵袭转移.
目的 探討Raf激酶抑製蛋白(RKIP)與肝細胞癌(HCC)侵襲轉移的關繫.方法 採用逆轉錄聚閤酶鏈反應(RT-PCR)方法檢測HCC、癌徬組織及正常肝組織中RKIP mRNA的錶達,採用免疫組織化學和Western blot法檢測不同肝組織中RKIP、p65和燐痠化細胞外調節蛋白激酶(pERK)蛋白的錶達,分析RKIP錶達與HCC臨床病理學特徵的關繫及其與p65和pERK錶達的相關性.結果 HCC、癌徬組織和正常肝組織中RKIP mRNA的錶達量分彆為1.357±0.569、1.512±0.623和1.550±0.426,組問差異無統計學意義(P>0.05).HCC、癌徬組織和正常肝組織中,RKIP蛋白的錶達量分彆為0.579±0.380、1.178±0.659和1.115±0.442,p65蛋白的錶達量分彆為0.830±0.376、0.630±0.337和0.466±0.345,pERK蛋白的錶達量分彆為1.023±0.478、0.605±0.367和0.461±0.293.免疫組織化學結果顯示,HCC、癌徬組織和正常肝組織中,RKIP的暘性錶達率分彆為22.2%、86.0%和93.8%,p65的暘性錶達率分彆為73.6%、56.0%和37.5%;pERK的暘性錶達率為65.3%、38.0%和31.3%.RKIP蛋白在HCC組織中的錶達顯著低于癌徬組織及正常肝組織,而p65和pERK在HCC組織中的錶達均顯著高于癌徬組織及正常肝組織(均P<0.05).RKIP蛋白錶達水平與HCC分化程度和有尤門靜脈或膽管癌柃情況有關(P<0.05),p65蛋白錶達水平與HCC分化程度和有無門靜脈或膽管癌栓有關,pERK蛋白錶達水平與HCC分化程度、有無門靜脈或膽管癌栓和肝內或淋巴結轉移情況有關(均P<0.05).HCC組織中RKIP的錶達與pERK的錶達相關(P=0.04),但與p65的錶達無關(P=0.143).結論 RKIP錶達的減少或缺失、p65和pERK的高錶達與HCC的髮生髮展、侵襲轉移密切相關.RKIP可能通過下調pERK的錶達抑製HCC的侵襲轉移.
목적 탐토Raf격매억제단백(RKIP)여간세포암(HCC)침습전이적관계.방법 채용역전록취합매련반응(RT-PCR)방법검측HCC、암방조직급정상간조직중RKIP mRNA적표체,채용면역조직화학화Western blot법검측불동간조직중RKIP、p65화린산화세포외조절단백격매(pERK)단백적표체,분석RKIP표체여HCC림상병이학특정적관계급기여p65화pERK표체적상관성.결과 HCC、암방조직화정상간조직중RKIP mRNA적표체량분별위1.357±0.569、1.512±0.623화1.550±0.426,조문차이무통계학의의(P>0.05).HCC、암방조직화정상간조직중,RKIP단백적표체량분별위0.579±0.380、1.178±0.659화1.115±0.442,p65단백적표체량분별위0.830±0.376、0.630±0.337화0.466±0.345,pERK단백적표체량분별위1.023±0.478、0.605±0.367화0.461±0.293.면역조직화학결과현시,HCC、암방조직화정상간조직중,RKIP적양성표체솔분별위22.2%、86.0%화93.8%,p65적양성표체솔분별위73.6%、56.0%화37.5%;pERK적양성표체솔위65.3%、38.0%화31.3%.RKIP단백재HCC조직중적표체현저저우암방조직급정상간조직,이p65화pERK재HCC조직중적표체균현저고우암방조직급정상간조직(균P<0.05).RKIP단백표체수평여HCC분화정도화유우문정맥혹담관암령정황유관(P<0.05),p65단백표체수평여HCC분화정도화유무문정맥혹담관암전유관,pERK단백표체수평여HCC분화정도、유무문정맥혹담관암전화간내혹림파결전이정황유관(균P<0.05).HCC조직중RKIP적표체여pERK적표체상관(P=0.04),단여p65적표체무관(P=0.143).결론 RKIP표체적감소혹결실、p65화pERK적고표체여HCC적발생발전、침습전이밀절상관.RKIP가능통과하조pERK적표체억제HCC적침습전이.
Objective To investigate the expression of RKIP, p65 and pERK in hepatoceUular carcinoma ( HCC) and their correlation with invasion and metastasis of HCC. Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK proteins in HCC tumor and peritumoral tissues were determined by immunohistochemistry and Western blot analysis. Statistical analysis was performed to determine the relationship between their expression and clinicopathological parameters. Results RKIP protein expression level (RKIP/actin) was 0.579 ±0.380 in HCCs, 1. 178 ±0.659 in peritumoral tissues and 1.115 ±0.442 in normal liver tissues. The pERK protein level was 1. 023 ± 0. 478, 0. 605 ± 0. 367 and 0. 461 ±0. 293, p65 protein level was 0. 83 ± 0.376, 0.63 ± 0.337 and 0.466 ± 0. 345, respectively. Immunohistochemistry analysis showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver tissues, were 22.2% , 86.0% , and 93.8% , positive rates of p65 were 73. 6% , 56. 0% and 37. 5% , positive rates of pERK were 65.3%, 38. 0% and 31.3%, respectively. Statistical analysis revealed that there was a significant difference in RKIP protein expression levels (P < 0.05), but no significant difference in RKIP mRNA expression levels (P>0.05) among HCC tumors, peritumoral tissues and normal liver tissues. The p65-positive and pERK-positive rates were higher in tumor tissues than that in peritumoral tissues and in normal liver tissues (P < 0.05 ) , but RKIP-positive rates were lower in tumor tissues than that in paritumoral tissues and normal liver tissues (P <0.05). RKIP protein expression levels were significantly lower in HCCs with intrahepatic or lymphatic metastasis than that in without. The RKIP positive rates in moderately and well differentiated HCCs were significantly higher than that in poorly differentiated HCCs. There was a relationship between RKIP and pERK expressions (P=0.04) , but RKIP expression was not correlated with p65 expression in HCCs (P = 0. 143). Conclusions Our findings indicate that the down-regulation of RKIP expression may serve as a predictive marker for HCC development, progression and metastasis, which may contribute to the elevated ERK activity. The inhibiting effect of RKIP on invasion and metastasis of liver cancer cells may be due to the down-regulation of pERK expression rather than p65 expression.
