熊跃Cancer Cell文章

　　

生物通报道，不久前参与指导复旦大学Science文章的复旦大学讲座教授熊跃教授在最近一期的Cell子刊Cancer Cell发表文章，CDK Inhibitor p18INK4c Is a Downstream Target of GATA3 and Restrains Mammary Luminal Progenitor Cell Proliferation and Tumorigenesis。

 

熊跃指导的复旦本土Science文章：复旦最新Science文章 发现新肿瘤抑制子

http://www.ebiotrade.com/newsf/2009-4/2009410153501.htm

 

此文章熊跃教授在美国北卡大学的研究团队完成，参与研究的还有来自哈佛大学医学院的研究人员。通讯作者是熊跃教授。

 

哺乳动物的上皮组织由luminal细胞和myoepithelial/basal细胞组成，一旦这些细胞癌变有可能转化成不同临床症状的乳腺癌。在本研究者，熊跃研究团队发现，小鼠缺乏CDK4/6 抑制子P18INK4c能自发的演变成ER阳性的luminal肿瘤。Ink4c缺乏刺激青春期的小鼠luminal祖细胞细胞增殖，这一促进作用会维持终身。

 

研究发现，GATA3能结合并抑制INK4c的转录。在人类的乳腺癌患者中，INK4低表达量和GATA3的高表达量会同时存在luminal A型肿瘤良性患者身上，这表明患者预后良好。

 

P18INK4c是GATA3的下游调节靶位，具有促使luminal祖细胞增殖的能力，并能抑制哺乳动物乳腺luminal祖细胞癌变。

（生物通  小茜）

 

生物通推荐原文检索：CDK Inhibitor p18INK4c Is a Downstream Target of GATA3 and Restrains Mammary Luminal Progenitor Cell Proliferation and Tumorigenesis

Xin-Hai Pei1,6,Feng Bai1,6,Matthew D. Smith1,Jerry Usary1,Cheng Fan1,Sung-Yun Pai5,I-Cheng Ho5,Charles M. Perou1,2,4andYue Xiong1,3,,

1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

2 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

3 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

4 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

5 Department of Pediatric Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, MA 02115, USA

6 These authors contributed equally to this work

 

【Summary】

Mammary epithelia are composed of luminal and myoepithelial/basal cells whose neoplastic transformations lead to distinct types of breast cancers with diverse clinical features. We report that mice deficient for the CDK4/6 inhibitor p18Ink4c spontaneously develop ER-positive luminal tumors at a high penetrance. Ink4c deletion stimulates luminal progenitor cell proliferation at pubertal age and maintains an expanded luminal progenitor cell population throughout life. We demonstrate that GATA3 binds to and represses INK4C transcription. In human breast cancers, low INK4C and high GATA3 expressions are simultaneously observed in luminal A type tumors and predict a favorable patient outcome. Hence, p18INK4C is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland.

 

熊跃教授1993年任美国北卡大学助理教授，1999年: 被北卡大学提升为副教授(终身)，2003年被北卡大学提升为正教授，2005年被北卡大学授予(William R. Kenan)教授称号。曾获北卡大学“Jefferson-Pilot奖”，“美国癌症协会青年研究人员奖”，“Pew学者奖”，“美国国防部乳腺癌研究职业发展奖”，“美国癌症研究协会Gertrude B. Elion研究奖”以及北卡大学“Hettleman学者成就奖”。现任北卡罗纳大学William R. Kenan教授，Lineberger癌症中心成员，“癌症研究”(Cancer Research) 资深编辑(Senior Editor), 分子与细胞生物学(Molecular and Cellular Biology) 编委, 细胞分裂(Cell Division) 编委, 及多家期刊和基金会不定期评审员。研究领域为细胞周期、肿瘤抑制、动物模式,蛋白泛素化。

 

代表论文

1.Zhang, Y, and Xiong, Y. (2001) A role of p53 N-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292:1910-1915

2.Liu, J, Furukawa, M, Matsumoto,T, Xiong, Y. (2002) NEDD8 modification of CUL1 dissociates p120CAND1, an inhibitor of CUL1-SKP1 binding and SCF ligases. Molecular Cell 10:1511-1518

3.Furukawa, M, He, YJ, Borchers, C, Xiong, Y. (2003) Targeting protein ubiquitination by BTB-cullin 3-Roc1 ubiquitin ligases. Nature Cell Biology 5:1001-1007

4.Hu, J, McCall, CM, Ohta, T, Xiong, Y. (2004) Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nature Cell Biology 6:1003-1009

5.He, Y., McCall, CM, Hu, J, Zeng Y, and Xiong Y. (2006) DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes & Development In press