P53 function and chemosensitivities of colon cancer

• Project/Area Number: 06670516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: GAMO Makio Institute of Development, Aging and Cancer, Tohoku University Assistant Professor, 加齢医学研究所, 講師 (00250829)
• Co-Investigator(Kenkyū-buntansha): KANAMARU Ryunosuke Institute of Development, Aging and Cancer, Tohoku University Professor, 加齢医学研究所, 教授 (70152783) ; MURAKAWA Yasuko Institute of Development, Aging and Cancer, Tohoku University Instructor, 加齢医学研究所, 助手 (50250832) ; 神部 真理子 (神戸 真理子) 東北大学, 加齢医学研究所, 講師 (00195190)
• Project Period (FY): 1994 – 1996
• Project Status: Completed (Fiscal Year 1996)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: anticancer drug / apoptosis / cell cycle / p53 / colon cancer / cultured cell line / 薬剤感受性

Research Abstract

The p53 protein is considered to play central roles in cell death pathways and regulation of cell cycle after DNA damages, causing apoptosis and/or cell cycle arrest through transactivation of effector protein such as p21. There was much evidence indicating that wild type p53 is required for the drug and radiaton induced normal tissue cell death. However it is still controversial whether p53 status of cancer cells is critical determinant of chemo-and radiosensitivities.
To elucidate this question, we checked the p53 status and chemosensitivities of twenty cultured cell lines. Using functonal analysis of separated alles in yeast (FASAY), two of the eight colon cancer, one of the six gastric cancer and three of six lung cancer cell lines found to exopress wild type p53. Chemosensitivities were by MTT assay using four anticancer drugs (5FU,CDDP,ADM,VP16). Two wild type colon cancer cell lines, LoVo and LS174T,were 5-20 times more chemosensitive than mutant ones, while no significant difference was found within chemosensitivities of gastric and lung cancer cell lines. As a result, p53 status might correlate with chemosensitivities in colon cancer cell lines, but not in gastric and lung cancers. Curiously, prominant drug induced apoptosis but no G1 arrest was induced in LoVo, the most chemosensitive cell line, while in LS174T,vice versa.Upregulation of p21 was comfirmed in both cell lines, suggesting some other factors are neccessary for p53 dependent apoptosis.

Research Products

• [Publications] Jia,L-Q,Osada,M,Ishioka,C,GAMOM.et al: "Screening the p53 status of human cell lines using a yeast functional assay" Molecular Carcinogenesis. (in press). (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Jia, L-Q., Osada, M., Ishioka, C., Gamo, M., Ikawa, S., Suzuki, T., Shimodaira, H., Niitani, T., and KUdo, T.: "Screening the p53 status of human cell lines using a yeast functonal assay." Molecular Carcinogenesis. (in press). (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Gamo, M., Ishioka, C., Jia, L.Q., Osada, M., Niitani, T., Sakayori, M., and Kanamaru, R.: "p53 function and chemosensitivities of colon cancer cell lines." Proceeding of the AACR. vol.37. 29 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jia, L-Q, Osaka, M Ishioka, C, GAMO, Metal: "Screening the p53 status of human cell lines using a yeast" Molecular Corcinogenesis. (in press). (1997)