COLLABORATION OF GROWTH FACTOR AND ONCOGENE PRODUCT IN HEPATOCARCINOGENESIS AND LIVER REGENERATION -ANALYSIS BY DOUBLE TRANSGENIC MICE-

生长因子和癌基因产物在肝癌发生和肝脏再生中的协同作用-双转基因小鼠分析-

基本信息

批准号：
09670510
负责人：
TAKAGI Hitoshi
金额：
$ 2.18万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670510/
关键词：
TGFalpha ras transgenic mice hepatoma TGFα

项目摘要

Transforming growth factor(TGF)alpha and protooncogene ras are involved inthe intracellular signal transduction through the activation of tyrosine kinase.We and other group have developed TGFalpha transgenic mice(T) and ras transgenicmice(R) independently, Both of the transgenic mice showed characteristicphenotypes e.g. hepatocellular carcinoma, pancreatic fibrosis for (T) andsplenic sarcoma and skin papilloma for (R). We made the double transgenic miceof TGFalpha and ras(T+R) and analyzed the phenotype, tumor formation, and liverregeneration. First of all, T+R had lower body weight than T and R and the rate ofliver weight! body weight was significantly higher in T+R than single T or R.Large hepato cellular carcinoma and adenoma were observed in 4 of 15 T+R 12months after birth. Four of 15(R) developed skin papilloma and 2 of 15 (T) didhepatic adenoma. More than 10% of hepatocytes were positively stained byproliferating cell nuclear antigen(PCNA) in liver tumors of T+R and about 1% ofnon-tumor tissue of T+R.On the other hand, non-tumor liver showed less than1% by PCNA.Compared with T and R, T+R showed enhanced regeneration of theliver after 2/3 hepatectomy. Skin tumor and splenic sarcoma was not enhancedin T+R compared with R.he weight of pancreas was heavier in T+R than T or Rand pancreatic fibrosis was enhanced in T+R than T or R.Thus simultaneous overexpression of TGFa and ras inhibited the growth ofthe mice and enhanced the growth of the liver, hepatic tumor formation andregeneration. Pancreatic fibrosis was also enhanced by TGFalpha and ras, resultingin enhanced growth of pancreas.

转化生长因子（TGF）α和原霉素RA通过激活酪氨酸激酶的激活参与细胞内信号转导。我们和其他组已经开发了TGFALPHA转基因小鼠（T）和RAS转基因学小鼠（R）独立于转质小鼠的特征性小鼠E.G.肝细胞癌，（T）和脾肉瘤和皮肤乳头状瘤（R）的胰腺纤维化。我们制作了TGFALPHA和RAS（T+R）的双转基因小鼠，并分析了表型，肿瘤形成和肝脏再生。首先，T+R的体重低于T和R，并且重量的速率！ T+R中的体重明显高于单个T或R.Large肝细胞癌，并且在出生后15个T+R 12个月中的4个中观察到腺瘤。 15（r）中有4个出现了皮肤乳头状瘤，其中2（t）中有2（t）didhepatic腺瘤。超过10％的肝细胞在T+R的肝脏肿瘤中呈阳性染色，在T+R的肝脏肿瘤和T+R.On的Non-肿瘤组织中约1％，非肿瘤肝脏表现出T+R的PCNA较小的1％，T+R，T+R显示出t+R的thefect and thefection thefection thefect thefect pcnefect after thefect pcnefect。与R.He胰腺的重量相比，T+R的重量与T+R或Rand Pancreatic纤维化相比，T+R中的T+R比T+R的T+R比T+R的胰腺重量更重，而T+r或R. tgfa的同时过表达TGFA和RAS抑制了小鼠的生长，而Liver tumor的生长和RAS增强了Tumor的生长和RAS。 TGFALPHA和RAS还增强了胰腺纤维化，导致胰腺的生长增强。