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Differential expression of cell cycle regulators in HCV-infection and related hepatocellular carcinoma

World Journal of Hepatology 2010年第1期2卷 32-41页

作者： Azza E El Bassiouny mona m Nosseir mona K Zoheiry Noha A Ameen Ahmed m Abdel-Hadi ibrahim.m.ibrahim.suher zada Abdel-Hakeem Saad El-Deen Nora E El-Bassiouni Department of Immunology Theodor Bilharz Research Institute Department of Pathology Central Laboratory Theodor Bilharz Research Institute Department of Hepato-Gastroenterology Theodor Bilharz Research Institute Biology Department American University Zoology Department Faculty of ScienceCairo University Department of Hematology Theodor Bilharz Research Institute

AIm:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. mETHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,*** wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal *** investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and *** D1 expressed nuclear staining that was sequentially increased from CHC to LC(Pmeanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 *** expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied *** analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC p

关键词： Chronic hepatitis C Liver cirrhosis Hepatocellular carcinoma Cell cycle Cyclin D1 Cyclin E p21 p27 Rb/p105

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