Evaluation of C/EBP(formula) as a candidate tumor suppressor gene in hepatocellular carcinoma
Author
Yuva, Yeliz
Advisor
Yakıcıer, M. Cengiz
Date
2004Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Hepatocellular carcinoma (HCC) is the fifth common type of cancer and third
leading cause of cancer deaths in the world. HCC is a genetically heterogeneous disease
and multiple pathways and molecules are identified to have role in development of
HCC. However, the molecular mechanisms underlying hepatocarcinogenesis are still
poorly understood.
The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is
important in differentiation of granulocytes, adipocytes and hepatocytes and mutations
in C/EBPα were described in acute myeloid leukemia. C/EBPα is strong inhibitor of cell
growth in liver and mouse lacking C/EBPα shows increased proliferation and phenotype
resembling HCC.
To clarify the role of C/EBPα in hepatocarcinogenesis, we analyzed the genetic
alterations of the C/EBPα in HCCs. We have screened C/EBPα mutations in HCC cell
lines and tumors by use of sequencing and heteroduplex analysis approaches. In HCC
cell lines and tumors, mutations and polymorphisms have been found. Thus, alterations
of C/EBPα are involved in hepatocellular carcinoma although it is not frequent. Ours is
the first report of C/EBPα alterations in HCC in our knowledge.