@techreport{oai:kindai.repo.nii.ac.jp:00014002, author = {樋口, 智紀 and 義江, 修 and 中山, 隆志}, month = {Jan}, note = {研究成果の概要(和文): これまでに我々は, 成人T細胞白血病/リンパ腫(ATL)や皮膚T細胞リンパ腫(CTCL)でFra-2が一貫して発現し, CCR4発現誘導や細胞増殖に関与することを明らかにしてきた. 本研究では, ATLとCTCL発癌におけるSOX4発現とその役割について検討した結果, ATLとCTCLにおいて, Fra-2-JunDが直接SOX4の転写活性を促進し, SOX4下流標的遺伝子として見出したGCKR, NAP1, HDAC8を発現誘導することでこれらの腫瘍の細胞増殖能を高めることを明らかにした. したがって, これらの知見からFra-2-SOX4経路はATLとCTCL発癌において重要な役割を有することが示唆された. 研究成果の概要(英文): Previously, we have shown that Fra-2 is consistently expressed and involved in CCR4 expression as well as cell growth in CCR4+ mature T-cell leukemias/lymphomas, including adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphomas (CTCLs). Here, we we examine the expression and function of SOX4 in the oncogenesis of ATL and CTCLs. Fra-2 and SOX4 were consistently co-expressed in the clinical samples of ATL and CTCL. SOX4 promoter analysis demonstrated that Fra-2-JunD directly activates the SOX4 promoter via an AP-1 site. Furthermore, SOX4 siRNA significantly suppressed cell growth of ATL and CTCL cell lines. We found that SOX4 knockdown reduced the expression of genes such as GCKR, NAP1 and HDAC8. We also showed direct activation of the HDAC8 promoter by SOX4. Furthermore, HDAC8 knockdown significantly suppressed cell growth of ATL and CTCL cell lines. Taken together, these finding suggest that the Fra-2-SOX4 pathway has an important oncogenic role in ATL and CTCLs., 研究種目:基盤研究(C); 研究期間:2011~2013; 課題番号:23591632; 研究分野:医歯薬学; 科研費の分科・細目:内科系臨床医学、皮膚科学, application/pdf}, title = {皮膚指向性成熟T細胞腫瘍においてFra-2-SOX4経路が担う発癌機構の解明}, year = {2013}, yomi = {ヒグチ, トモノリ and ヨシエ, オサム and ナカヤマ, タカシ} }