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学科主题: 临床医学
题名:
SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30(+) lymphoproliferative disease by repressing p21
作者: Wang, Yang1; Gu, Xiaoguang1; Zhang, Gaolei1; Wang, Lin2; Wang, Tingting2; Zhao, Yun3; Zhang, Xiuyan3; Zhou, Youwen4; Kadin, Marshall5; Tu, Ping1
刊名: BLOOD
发表日期: 2014-05-29
DOI: 10.1182/blood-2013-10-534693
卷: 123, 期:22, 页:3452-3461
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology
研究领域[WOS]: Hematology
关键词[WOS]: BINDING-PROTEIN 1 ; LYMPHOMATOID PAPULOSIS ; GENE-EXPRESSION ; MYCOSIS-FUNGOIDES ; SEZARY-SYNDROME ; MULTIPLE GENES ; CANCER ; DISORDERS ; DIFFERENTIATION ; PROGRESSION
英文摘要:

Cutaneous CD30(+) lymphoproliferative disease (CD30(+) LPD), characterized by the presence of CD30(+) anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). However, little is known about the pathobiology of the CD30(+) lymphoma cells, as well as the mechanisms of disease progression. Here we report that Special AT-rich region binding protein 1 (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30(+) lymphoma cells in most CD30(+) LPDs, and its expression is upregulated during disease progression. Our findings show that SATB1 silencing in CD30(+) LPD cells leads to G1 cell cycle arrest mediated by p21 activation. Using chromatin immunoprecipitation, luciferase assays, and mutational analysis, we demonstrate that SATB1 directly regulates the transcription of p21 in a p53-independent manner. Moreover, DNA demethylation on a specific CpG-rich region of the SATB1 promoter is associated with the upregulation of SATB1 during disease progression. These experiments define a novel SATB1-p21 pathway in malignant CD30(+) T lymphocytes, which provides novel molecular insights into the pathogenesis of CD30(+) LPDs and possibly leads to new therapies.

语种: 英语
所属项目编号: 81072233 ; 81201228 ; 115138
项目资助者: National Nature Science Foundation of China ; Canadian Institute of Health Research
WOS记录号: WOS:000342616600020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63738
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Peking Univ, Dept Dermatol & Venerol, Hosp 1, Beijing 100034, Peoples R China
2.Sichuan Univ, West China Hosp, Dept Dermatovenereol, Chengdu 610064, Sichuan, Peoples R China
3.Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou, Peoples R China
4.Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada
5.Boston Univ, Sch Med, Dept Dermatol & Skin Surg, Roger Williams Med Ctr, Providence, RI USA

Recommended Citation:
Wang, Yang,Gu, Xiaoguang,Zhang, Gaolei,et al. SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30(+) lymphoproliferative disease by repressing p21[J]. BLOOD,2014,123(22):3452-3461.
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