[Reduced expression of the E3-ubiquitin ligase seven in absentia homologue (SIAH)-1 in human hepatocellular carcinoma].
SIAH-1 (seven in absentia homologue-1) is an E3-ubiquitin ligase that facilitates labelling and subsequent proteasomal degradation of different proteins like transcription factors (e.g. c-myb) and coactivators (e.g. beta-catenin). Here we show that SIAH-1 expression is frequently reduced in human hepatocarcinogenesis. However, further reduction of SIAH-1 bioavailability by gene-specific siRNA (RNAinterference) in HCC cell lines resulted in significantly decreased tumor cell viability. Therefore we conclude that distinct SIAH-1 levels mediate pro-tumorigenic effects in HCC cells and that further SIAH-1 inhibition may represent a new therapeutic strategy in the treatment of human hepatocellular carcinoma.
Brauckhoff
A
A
Pathologisches Institut, Universititsklinikum Heidelberg.
Ehemann
V
V
Schirmacher
P
P
Breuhahn
K
K
D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics*; D012016:Reference Values; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000098563:Seven in Absentia Proteins
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins