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和原癌基因ras通过酪氨酸激酶的激活参与细胞内信号转导。我们和其他课题组独立培育了TGFα转基因小鼠(T)和ras转基因小鼠(R)，两种转基因小鼠均表现出特征性表型例如肝细胞癌、胰腺纤维化（T），脾肉瘤和皮肤乳头状瘤（R）。我们制作了TGFα和ras(T+R)双转基因小鼠，并分析了其表型、肿瘤形成和肝脏再生。首先，T+R的体重和肝重率均低于T和R！ T+R组体重明显高于单次T或R组。出生后12个月，15例T+R组中有4例出现大肝细胞癌和腺瘤。 15 名 (R) 中的 4 名出现皮肤乳头状瘤，15 名 (T) 中的 2 名出现双肝腺瘤。 T+R肝肿瘤组织中10%以上肝细胞呈增殖细胞核抗原（PCNA）阳性，T+R非肿瘤组织中约1%肝细胞呈增殖细胞核抗原（PCNA）阳性。 PCNA。与T和R相比，T+R显示2/3肝切除后肝脏再生增强。与R相比，T+R中皮肤肿瘤和脾肉瘤没有增强。T+R中胰腺重量比T或R重，并且T+R中胰腺纤维化比T或R中增强。因此TGFa和ras同时过表达受到抑制促进小鼠的生长并增强肝脏的生长、肝肿瘤的形成和再生。 TGFα 和 ras 也可增强胰腺纤维化，从而促进胰腺生长。