title: E2F-1 is overexpressed and pro-apoptotic in human hepatocellular carcinoma.
abstract: E2F-1 is a transcription factor involved in DNA synthesis and repair, cell proliferation, and apoptosis. Hyposphorylated pRb represses E2F-1 action in early G1 phase, while in late G1, pRb hyperphosphorylation leads to E2F-1 release and activation. In vitro studies have shown that E2F-1 may act either as oncogene or as tumor suppressor gene. We evaluated immunohistochemical expression of E2F-1 protein in chronic viral liver disease and hepatocellular carcinoma (HCC) and correlated this with clinicopathological parameters, cell proliferation, apoptosis, and the expression of E2F-1-regulators, pRb, and phospho-pRb (Ser795). In liver biopsies from 30 patients with chronic viral hepatitis, including 22 with cirrhosis without HCC, and 57 with cirrhosis with HCC, E2F-1 expression was assessed by immunohistochemistry. In chronic hepatitis and cirrhosis, hepatocytes and cholangiocytes demonstrated mild cytoplasmic and/or nuclear membrane E2F-1 immunostaining. In contrast, all HCC (100 %) showed strong nuclear E2F-1 immunostaining, with or without membrane accentuation, while a minority demonstrated additional moderate cytoplasmic immunostaining. Abnormally low pRb and phospho-pRb expression was seen in 70 % and 67.9 % of HCC, respectively. In HCC, nuclear E2F-1 expression was inversely correlated with phospho-pRb expression (p = 0.001) and positively related to tumor apoptotic index (p = 0.025). No significant correlation was found between E2F-1 expression and patient demographics, HCC etiology, tumor grade, pRb, p53 expression, or cell proliferation. In conclusion, we show that the increased expression of E2F-1 protein in human HCC is correlated with enhanced tumor cell apoptosis supporting a pro-apoptotic role of E2F-1 in human HCC.
authors.affiliation: Laboratory of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str, Goudi, Athens 11527, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Palaiologou
authors.forename: John
authors.initials: J
authors.lastname: Koskinas
authors.forename: Menelaos
authors.initials: M
authors.lastname: Karanikolas
authors.forename: Evangelia
authors.initials: E
authors.lastname: Fatourou
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading
chemical_list: D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human