Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin.
Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of apoptosis and cell proliferation. Overexpression of survivin has been implicated in several human cancers, including human hepatocellular carcinoma (HCC). Although several factors have been shown in vitro to upregulate survivin expression in cancer cells, the in vivo regulators of survivin in human hepato-carcinogenesis are largely unknown. We studied by immunohistochemistry the protein expression of survivin in relation to cyclin D1, phosphorylated signal transducer and activator of transcription 3 (p-STAT3), beta-catenin, E-cadherin and phosphorylated-Akt (p-Akt) in 69 cases of HCC and adjacent liver cirrhosis. Survivin was expressed in 63/69 (91.3%) cases of HCC and in 40/47 (85.1%) cases of liver cirrhosis. Survivin localization in HCC was exclusively nuclear, while intense cytoplasmic and low nuclear expression of survivin was observed in cases of cirrhosis. Survivin expression in HCC correlated significantly with low grade tumors, expression of cyclin D1 and p-STAT3. Expression of survivin in liver cirrhosis correlated with downregulation of E-cadherin expression. There was no significant correlation of survivin with beta-catenin or p-Akt in HCC or liver cirrhosis. In conclusion, we showed an association of nuclear survivin with well differentiated HCC, as well as with the expression of the cell cycle regulator cyclin D1. Activation of STAT3 and loss of E-cadherin but not beta-catenin or Akt pathways seem to be implicated in survivin upregulation in HCC and liver cirrhosis.
Peroukides
Stavros
S
Department of Anatomy, School of Medicine, University of Patras, Rio, Patras, Greece.
Bravou
Vasiliki
V
Alexopoulos
Alexandros
A
Varakis
John
J
Kalofonos
Haralabos
H
Papadaki
Helen
H
D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D018709:Statistics, Nonparametric; D000077022:Survivin; D051176:beta Catenin / Q000378:metabolism
C107489:BIRC5 protein, human; D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D000077022:Survivin; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt