2013 Fiscal Year Final Research Report
The role of Fra-2 and SOX4 oncogene cascade in ATL and CTCLs
| Project/Area Number |
23591632
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIE Osamu 近畿大学, 医学部, 教授 (10166910)
NAKAYAMA Takashi 近畿大学, 薬学部, 教授 (60319663)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 皮膚腫瘍学 / SOX4 / Fra-2 / 成人T細胞白血病／リンパ腫（ATL） / 皮膚T細胞リンパ腫（CTCL） |
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| Research Abstract |
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.
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