Oncogenic functions of the WT1 gene in leukemia

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: OJI Yusuke 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (20294100)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: WT1 / oncogene / chemoresistance

Outline of Final Research Achievements

The WT1 gene is overexpressed in leukemia and various types of solid tumors.In the present research project, we elucidated two novel mechanisms by which WT1 exerts its oncogenic functions. First, WT1 induced resistance to chemotherapeutic drugs such as DOX through promotion of homologous recombination (HR) that plays a critical role in DNA damage repair responses. Among four isoforms of WT1, WTC isoform alone promoted HR, which resulted from upregulation of HR factors, XRCC2, Rad51D, and Rad54. Immunohistochemistry showed that XRCC2 and Rad54 proteins were highly expressed in the majority of NSCLC and gastric cancer, and that expression of these two proteins was significantly correlated with that of WT1 protein in NSCLCs. Second, we showed the involvement of cytoplasmic WT1 protein in metabolic regulation through direct binding to metabolic enzymes in tumor cells. These interactions of WT1 with metabolic enzymes might be targets of novel molecular targeted cancer therapy.

Free Research Field

腫瘍生物学　血液学　腫瘍免疫学