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1998 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 09670510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionGUNMA UNIVERSITY

Principal Investigator

TAKAGI Hitoshi  GUNMA UNIVERSITY SCHOOL OF MEDICINE,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,TEACHING ASSOCIATE, 医学部, 助手 (20251093)

Project Period (FY) 1997 – 1998
KeywordsTGFalpha / ras / transgenic mice / hepatoma
Research Abstract

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.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Takagi, H, et al: "Histochemical analysis of the hyperplastic stomach of TGFα transgenic mice." Dig Dis Sciences. 42. 91-98 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi H, et al: "A new point mutation in cholinesterase : relationship between multiple mutation site and enzyme activity." Iat Hepatol Commun.6. 288-293 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi H, et al: "Steroid hormone-dependent overexpression of cytochrome p4502A in liver tumor of TGFα transgenic mice." J Gastroeuterol. 32. 708-711 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi H, et al: "Accidental transmission of hepatitis C and treatment with interferon." J Gastroeuterol Hepatol. 13. 238-243 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi H, et al: "Prediction of the effect of interferon to chronic hepatitis C." Dig Dis Sciences. 42. 2270-2276 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakizaki S, et al: "The natural history of untreated hepatocellular carcinoma." Int J clin Oucol. 3. 299-303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi H,et al: "Histochemical analysis of the hyperplastic stomach of TGFalpha transgenic mice." Dig Dis Sciences. 42. 91-98 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi H,et al: "Steroid hormone-dependent overexpression of the cytochrome p450 2A in liver tumors of TGFalpha transgenic male mice." J Gastroenterology. 32. 708-711 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takayama H,et al: "Analysis of the hepatic and gastrointestinal phenotype of HGF/SF transgenic mice.(in Japanese)" Frontiers in Gastroenterology. 2. 252-260 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi H,et al: "Prediction of the effect of Interferon to chronic hepatitis C." Dig Dis Sciences. 42. 2270-2276 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi H,et al: "Accidental transmission of hepatitis C." J Gastroenterol Hepatol. 13. 238-243 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakizaki S,et al.: "Hepatocellular carcinoma associated with extrahepatic primary malignant neoplasms." Int J Clin Oncol.3. 204-208 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakizaki S,et al.: "The natural history of untreated hepatocellular carcinoma." Int J Clin Oncol.3. 299-303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichikawa, et al.: "Quantitative analysis of hepatitis B virus precore mutant in hepatitis B." Tohoku J Exp Med. 186. 323-333 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kojima A,et al.: "Survival of patient with late onset hepatic failure by living related liver transplantation from maternal donor with incompatible blood type." J Gastroenterol. 33. 899-903 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi H,et al: "Androgen dependency in hepatocarcinogenesis of TGFa transgenic mice." Intenational Association of For The Study of The Liver.November 4,1998. Hepatology Supple 176A Support Care Cancer (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sohara N,et al.: "Nausea and vomiting induced by arterial chemo-embolization in patients with hepatocellular carcinoma and the antiemetic effect of ondansetron hydrchrolide."

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakizaki S,et al.: "The Efficacy of twice-a day treatment of inteferon beta for chronic hepatitis C." J Viral Hepatitis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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