The role of Fra-2 and SOX4 oncogene cascade in ATL and CTCLs

Fra-2 和 SOX4 癌基因级联在 ATL 和 CTCL 中的作用

• 批准号: 23591632
• 负责人: HIGUCHI Tomonori
• 金额: $ 3.08万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591632/
• 关键词: 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）; HDAC8; ATL; CTCL; ATLL

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.

之前，我们已经证明Fra-2在CCR4+成熟t细胞白血病/淋巴瘤（包括成人t细胞白血病/淋巴瘤（ATL）和皮肤t细胞淋巴瘤（ctcl））中一致表达并参与CCR4表达和细胞生长。在这里，我们研究了SOX4在ATL和ctcl肿瘤发生中的表达和功能。Fra-2和SOX4在ATL和CTCL的临床样本中一致共表达。SOX4启动子分析表明，fr -2- jund通过AP-1位点直接激活SOX4启动子。此外，SOX4 siRNA显著抑制ATL和CTCL细胞系的细胞生长。我们发现SOX4的敲低降低了GCKR、NAP1和HDAC8等基因的表达。我们还发现SOX4可以直接激活HDAC8启动子。此外，HDAC8敲低显著抑制ATL和CTCL细胞系的细胞生长。综上所述，这些发现提示fr -2- sox4通路在ATL和ctcl中具有重要的致癌作用。

项目成果

Generation of colonic IgA-secreting cells in the caecal patch

• DOI: 10.1038/ncomms4704
• 发表时间: 2014-04-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Masahata, Kazunori;Umemoto, Eiji;Takeda, Kiyoshi
• 通讯作者: Takeda, Kiyoshi

Selective down-regulation of Th2 cell-mediated airway inflammation in mice by pharmacological intervention of CCR4

• DOI: 10.1111/j.1365-2222.2011.03847.x
• 发表时间: 2012-02-01
• 期刊: CLINICAL AND EXPERIMENTAL ALLERGY
• 影响因子: 6.1
• 作者: Kaminuma, O.;Ohtomo, T.;Hiroi, T.
• 通讯作者: Hiroi, T.

Expression and Function of FRA2/JUND in Cutaneous T-Cell Lymphomas.

FRA2/JUND 在皮肤 T 细胞淋巴瘤中的表达和功能。

• 发表时间: 2012
• 期刊: Anticancer Research
• 影响因子: 2
• 作者: 清田政宏;須藤祐人;秋山弘匡;田代文夫;Takashi Nakayama et al.
• 通讯作者: Takashi Nakayama et al.

c-Maf suppresses human T-cell leukemia virus type 1 Tax by competing for CREB-binding protein

c-Maf 通过竞争 CREB ​​结合蛋白抑制人类 T 细胞白血病病毒 1 型 Tax

• DOI: 10.1111/j.1349-7006.2011.01873.x
• 发表时间: 2011
• 期刊: Cancer Sci
• 影响因子: 5.7
• 作者: Hieshima K;Nagakubo D;Shigeta A;Tanaka Y;Hoshino H;Tsukasaki K;Yamada Y;Yoshie O
• 通讯作者: Yoshie O

The chemokine superfamily revisited.

• DOI: 10.1016/j.immuni.2012.05.008
• 发表时间: 2012-05-25
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Zlotnik A;Yoshie O
• 通讯作者: Yoshie O