Activation of the p53 pathway by gene medicine and a chemotherapeutic agent produces anti-tumor effects on human mesothelioma cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591185
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: MASATO Shingyoji 千葉県がんセンター(研究所), その他部局等, その他 (60450433)
• Co-Investigator(Kenkyū-buntansha): TAGAWA Masatoshi 千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 悪性中皮腫 / アデノウイルス / p53経路 / アポトーシス / ビスフォスフォネート

Outline of Final Research Achievements

We examined a possible therapeutic strategy for mesothelioma, which is linked with asbestos exposure. A major genetic characteristic of the clinical specimens is a deletion of p14 and p16 genes, which subsequently inactivate the p53 and the pRb pathways. We thereby targeted the p53 pathway and reconstituted the functions by gene transduction with a few kinds of adenovirus vectors. The adenovirally transduced cells showed apoptotic cell death accompany by phosphorylation of p53 and dephosphorylation of pRb. We also found that bisphosphonates, commonly used for malignancy-linked hypercalcemia and for osteoporosis, was highly cytotoxic to mesothelioma. The agent is inhibits prenylation of small G proteins and subsequently suppress the functions. The cells treated with bisphosphonates were subjected to apoptotic cell death with activation of the p53 pathways.

Free Research Field

呼吸器内科