Development of a novel approach to hepatocellular carcinoma

• Project/Area Number: 08670616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jichi Medical School
• Principal Investigator: MANO Hiroyuki Jichi Medical School, Faculty of Medicine Associate Professor, 医学部, 助教授 (90240704)
• Project Period (FY): 1996 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: hepatocellular carcinoma / alpha fetoprotein / 自殺遺伝子 / アルファフェトプロティン

Research Abstract

We have currently only a few ways to treat hepatocellular carcinoma (HCC). To develop a novel approach to treat HCC,we have here investigated whether the promoter of alpha feto-protein (AFP) gene can confer a tumor-specific expression of the cytosine deaminase (CD) gene. The AFP promoter fragment of 1.2 kbp was ligated with the CD cDNA or the reporter luciferase cDNA.These expression cassettes were subcloned into a retroviral vector plasmid, pLNSX,and were used to generate recombinant retroviruses.
Infection of AFP-luciferase retrovirus resulted in the AFP-producing cell-specific expression of luciferase. Furthermore, addition fo 5'-fluorocytosine into the culture media induced apoptosis only in the AFP-producing HCC cell lines, but not in 3T3 or Hela cells. Taken together, our data prove that the AFP-promoter can become a useful tool to confer tumor-specific suicide in HCC cells.

Research Products

• [Publications] Kitanaka, A., et al.: "Expression and activation of the nonreceptor tyrosine kinase Tec in humen B cells" Blood. 91. 940-948 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ohya, K., et al.: "SOCS-1/JAB/SSI-1 can bind and suppress Tec protein-tyrosin Kinase" J.Biol.Chem.272. 27178-27182 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ito, K., et al.: "Development a novel selective amplifier gene for controllable expansion of transduced hematopoietic cells" Blood. 90. 3884-3892 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamashita, Y., et al.: "Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway" Exp.Hematol.25. 211-216 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitanaka, A., Mano, H., Conley, M.E.and Campana, D.: "Expression and activation of the nonreceptor tyrosine kinase Tec in human B cells" Blood. 91. 940-948 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ohya, K., Kajigaya, S., Yamashita, Y., Miyazato, A., Hatake, K., Miura, Y., Ikeda, U., Shimada, K., Ozawa, K.and Mano, H.: "SOCS-1/JAB/SSI-1 can bind and suppress Tec protein-tyrosine kinase" J.Biol.Chem.272. 27178-27182 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ito, K., Ueda, Y., Kokubun, M., Urabe, M., Inaba, T., Mano, H., Hamada, H., Kitamura, T., Mizoguchi, H., Sakata, T., Hasegawa, M.and Ozawa, K.: "Development of a novel selective amplifier gene for controllable expansion of transduced hematopoietic cells" Blood. 90. 3884-3892 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamashita, Y., Miyazato, A., Shimizu, R., Komatsu, N., Miura, Y., Ozawa, K.and Mano, H.: "Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mp1 signaling pathway" Exp.Hematol.25. 211-216 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kitanaka,A.: "Expression and activation of the nonvecepter tyrosine kinase tec in human B cells" Blood. 91. 940-948 (1998)
• [Publications] Ohya,K.: "SOCS-1/JAB/SSI-1 can bind and suppress Tec protein-tyrosine kinase" J.Biol.Chem.272. 27178-27182 (1997)
• [Publications] Ito,K.: "Development of a novel selective amplitier gene for controllable expansion of transduced hematopoietic cells" Blood. 90. 3884-3892 (1997)
• [Publications] Yamashita,Y.: "Tec protein-tyrosine kinase is involved in the thrombopoietin le-Mpl signaling pathway" Exp.Hematol.25. 211-216 (1997)
• [Publications] Mano,H.: "Tec protein-tyrosine kinase is an effector molecule of Lyn protein-tyrosine kinase" FASEB J.10. 637-642 (1996)
• [Publications] Miyazato,A.: "Tec protein-tyrosine kinase is involved in the signaling mechanism of granulocyte colony stimulating factor receptor" Cell Growth Differ.7. 1135-1140 (1996)
• [Publications] Yamashita,Y.: "Deletion of Src homology 3 domain results in unstitutive activation of Tec protein-tyrosine kinase" Jpn.J.Cancer Res.87. 1106-1110 (1996)
• [Publications] Yamashita,Y.: "Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway" Exp.Hematol.(in press).
• [Publications] Kazama,A.: "High expression of the tec gene product in murine testicular germ cells and erythroblasts" Pathol.Int.46. 341-347 (1996)
• [Publications] Honda,H.: "Cloning and characterization of mouse tec promoter" Biochem.Biophys.Res.Commun.223. 422-426 (1996)