@article{3089833,
    title = "E2F-1 is overexpressed and pro-apoptotic in human hepatocellular carcinoma",
    author = "Palaiologou, M. and Koskinas, J. and Karanikolas, M. and Fatourou, E. and Tiniakos, D.G.",
    journal = "Virchows Archiv",
    year = "2012",
    volume = "460",
    number = "5",
    pages = "439-446",
    issn = "0945-6317, 1432-2307",
    doi = "10.1007/s00428-012-1220-4",
    keywords = "protein p53;  retinoblastoma protein;  transcription factor E2F1, adult;  aged;  apoptosis;  article;  cancer grading;  cell nucleus membrane;  cell proliferation;  chronic hepatitis;  clinical article;  controlled study;  cytoplasm;  female;  histopathology;  human;  human cell;  human tissue;  immunohistochemistry;  liver biopsy;  liver carcinogenesis;  liver cell;  liver cell carcinoma;  liver cirrhosis;  male;  priority journal;  protein expression;  protein phosphorylation;  tumor cell;  virus hepatitis, Adult;  Aged;  Apoptosis;  Carcinoma, Hepatocellular;  Cell Proliferation;  E2F1 Transcription Factor;  Female;  Humans;  Immunohistochemistry;  Liver Cirrhosis;  Liver Neoplasms;  Male;  Middle Aged;  Neoplasm Grading;  Tumor Markers, Biological",
    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 (p00.001) and positively related to tumor apoptotic index (p00.025). 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. © Springer-Verlag 2012."
}