Expression analysis of DoK-1, Dok-2 and Dok-3 genes in mice expressing Tax, a human T-cell leukemia virus type 1 oncoprotein

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Rakuno Gakuen University
• Principal Investigator: Ohsugi Takeo 酪農学園大学, 獣医学群, 教授 (00211102)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: HTLV-1 / Tax / 成人T細胞白血病 / Dok-1 / Dok-2 / Dok-3

Outline of Final Research Achievements

Human T-cell leukemia virus type 1 (HTLV-1) can cause adult T-cell leukemia/lymphoma (ATL). The Tax protein encoded by HTLV-1 appears to be a key element in the early stage of ATL development. We examined the expression of the downstream of tyrosine kinase (Dok) family members Dok-1, Dok-2 and Dok-3, recently reported to be tumor suppressors, in HTLV-1-infected T cells and transgenic mice expressing the tax gene. Dok-2 and Dok-3 expression was significantly reduced in HTLV-1-infected T cells compared with their expression in uninfected T cells, and the expression of Dok-3 was reduced by the induction of Tax expression in T cells. The transgenic mice showed low expression of Dok-1, Dok-2 and Dok-3 in mice with T cell leukemia. Mice showed low Dok-2 expression at 5-6 months of age before disease onset. These results suggest that downregulation of Dok-2 and Dok-3 by the expression of the viral tax gene is the first step in the development of ATL.

Free Research Field

実験動物学