Analysis of anti-tumor effect of HGF in transgenic mice

HGF对转基因小鼠的抗肿瘤作用分析

• 批准号: 07807057
• 负责人: SHIOTA Goshi
• 金额: $ 1.34万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807057/
• 关键词: HGF; hepatocellular carcinoma; anti-tumor effect; liver metastasis; double transgenic mice; 肝細胞癌; 肝転移

Since we developed transgenic mice expressing HGF in liver (G.Shiota et al.Hepatology 19,962-972,1994), we have studied anti-tumor effect of HGF by using transgenic mice. First, we studied metastatic potentials of hepatocellular carcinoma (HCC) cells in chimeric mice of HGF transgenic and nude. Second, we have developed 2 kinds of double transgenic mice of HGF with TGFalpha and c-myc, and have evaluated effect of HGF on TGFalpha-or c-myc-induced hepatocarcinogenesis.1. Metastatic potential of HCC cells, such as HUH7, Hep3B and FaO cells, via portal vein was greatly suppressed in HGF/nude chimeric mice compared to nude control mice (81% vs.35%, p<0.05). 2. Double transgenic mice of TGFalpha and HGF developed HCC in 33% of mice, whereas TGFalpha mice developed HCC in 60% of mice. 3. Although c-myc mice developed adenoma and HCC in 92% and 58% of mice, HGF/c-myc double transgenic mice did 33% and 0%, respectively.

自从我们开发了在肝脏中表达HGF的转基因小鼠（G.Shiota等，Hepatology 19，962 - 972，1994）以来，我们通过使用转基因小鼠研究了HGF的抗肿瘤作用。首先，我们研究了肝细胞癌（HCC）细胞在HGF转基因与裸小鼠嵌合体中的转移潜能。第二，我们建立了两种HGF与TGF α和c-myc双转基因小鼠，并评价了HGF对TGF α和c-myc诱导的肝癌发生的影响。与裸对照小鼠相比，HGF/裸嵌合体小鼠中HCC细胞（例如HUH 7、Hep 3B和FaO细胞）通过门静脉的转移潜力被极大地抑制（81%对35%，p<0.05）。2. TGF α和HGF双转基因小鼠中33%的小鼠发生了HCC，而TGF α小鼠中60%的小鼠发生了HCC。3.虽然c-myc小鼠中92%和58%的小鼠发生腺瘤和HCC，但HGF/c-myc双转基因小鼠分别为33%和0%。

项目成果

G.Shiota et al: "Characterization of double transgenic mice expressing hepstoyte growth factor and transforming growth factorα" Res.Commun.Mol.Pathol.Pharmacal.90. 17-24 (1995)

G. Shiota 等人：“表达庚细胞生长因子和转化生长因子 α 的双转基因小鼠的特征”Res.Commun.Mol.Pathol.Pharmacal.90 (1995)。

E.Santon-Rugi et al: "Inhibition of neoplastic development in the liver by hepatoyte growth factor in a transgenic mouse model." Proc.Natl.Acad.Sci USA. 93. 9577-9582 (1996)

E.Santon-Rugi 等人：“在转基因小鼠模型中肝细胞生长因子抑制肝脏肿瘤的发展。”

G.Shiota et al.: "Down-regulation of c-myc mRNA after completton of liver regeneration in transgenic mice expressing hepatocyte growth factor in liver" Res.Commun.Mol.Pathol.Pharmacol.89. 259-268 (1995)

G.Shiota 等人：“肝脏中表达肝细胞生长因子的转基因小鼠完成肝再生后 c-myc mRNA 的下调”Res.Commun.Mol.Pathol.Pharmacol.89。

G.Shiota et al.: "Inhibitory effect of hepatocyte growth factor on metastasis of hepatocellular carciuana in transgenic nice" Res.Commun.Mol.Pathol.Pharmacol.91. 33-39 (1996)

G.Shiota 等人：“肝细胞生长因子对转基因尼斯肝细胞癌转移的抑制作用”Res.Commun.Mol.Pathol.Pharmacol.91。

J.Okano et al.: "Protective action of hepatocyte growth factor for acute liver injury caused by D-galactosamine in transgenic mice" Hepatology. 26. 1241-1249 (1997)

J.Okano 等人：“肝细胞生长因子对转基因小鼠中由 D-半乳糖胺引起的急性肝损伤的保护作用”肝病学。