| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The goal of this research project is to elucidate that the direction of tumor differentiation is one of important factors that provide the biological behavior of tumor cells.
We mainly examined the role of CCAAT/enhancer binding protein (C/EBP)-β, one of liver enriched transcription factors, and its isoforms (LAP and LIP) in three different experimental designs
1)AFP-producing gastric carcinoma cells are the gastric carcinoma model with hepatic phenotype. We confirmed the hepatic phenotype by the liver-specific protein expression, such as albumin, in AFP-producing gastric carcinoma cells. We observed LAP, the activated isoform, was predominantly expressed in AFP-producing gastric carcinoma cells, whereas LIP, the inhibitory isoform, was predominantly in control gastric cells. The introduction of LIP in AFP-producing gastric carcinoma cells demonstrated the partially reduction of hepatic phenotypes.
2)Rat pancreatic tumor cell, AR42J-B13, is a unique cell that transdifferentiats from pancreas to liver. Introduction of C/EBP-β demonstrated the induction of the hepatic phenotype. The transfected cells were resistant to the serum cytotoxicity in vitro, and less apoptotic in the liver sinusoid after intra-portal injection than control cells.
3)AT-2-TC, a rat yolk sac tumor cell, was introduced by C/EBP-β, because hepatoid differentiation is occasionally seen in yolk sac tumor. The expression of serum protein including AFP was induced in the transfectant. The liver-enriched transcription factors, HNF-1a, -1b, and -4 were also induced. This induction was only seen in the xenograft in mice, in which C/EBP-β was phosphorylated.
Correcting these findings, it was assumed that C/EBP-β may contribute the modulation of the differentiation of tumor cells.
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