Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia

被引：212

作者：

Keeshan, Karen

He, Yiping

Wouters, Bas J.

Shestova, Olga

Xu, Lanwei

Sai, Hong

Rodriguez, Carlos G.

Maillard, Ivan

Tobias, John W.

Valk, Peter

Carroll, Martin

Aster, Jon C.

Delwel, Ruud

Pear, Warren S. ^{[1
]}

机构：

[1] Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Erasmus MC, Dept Hematol, NL-3015 GE Rotterdam, Netherlands

[3] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA

[4] Univ Penn Bioinformat Core, Philadelphia, PA 19104 USA

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

CANCER CELL | 2006年 / 10卷 / 05期

关键词：

D O I：

10.1016/j.ccr.2006.09.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tribbles homolog 2 (Trib2) was identified as a downregulated transcript in leukemic cells undergoing growth arrest. To investigate the effects of Trib2 in hematopoietic progenitors, mice were reconstituted with hematopoietic stem cells retro-virally expressing Trib2. Trib2-transduced bone marrow cells exhibited a growth advantage ex vivo and readily established factor-dependent cell lines. In vivo, Trib2-reconstituted mice uniformly developed fatal transplantable acute myelogenous leukemia (AML). In mechanistic studies, we found that Trib2 associated with and inhibited C/EBP alpha. Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBP alpha.

引用

页码：401 / 411

页数：11

共 50 条

[1] A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K
Traver, D
Miyamoto, T
Weissman, IL
[J]. NATURE, 2000, 404 (6774) : 193 - 197
[2] Generation of truncated C/EBPβ isoforms by in vitro proteolysis
Baer, M
Johnson, PF
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) : 26582 - 26590
[3] Expression profiles of androgen independent bone metastatic prostate cancer cells indicate up-regulation of the putative serine-threonine kinase GS3955
Bisoffi, M
Klima, I
Gresko, E
Durfee, PN
Hines, WC
Griffith, JK
Studer, UE
Thalmann, GN
[J]. JOURNAL OF UROLOGY, 2004, 172 (03) : 1145 - 1150
[4] SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia
Bowers, AJ
Scully, S
Boylan, JF
[J]. ONCOGENE, 2003, 22 (18) : 2823 - 2835
[5] Calkhoven CF, 2000, GENE DEV, V14, P1920
[6] Induction of C/EBPα activity alters gene expression and differentiation of human CD34+ cells
Cammenga, J
Mulloy, JC
Berguido, FJ
MacGrogan, D
Viale, A
Nimer, SD
[J]. BLOOD, 2003, 101 (06) : 2206 - 2214
[7] Notch signaling is necessary but not sufficient for differentiation of dendritic cells
Cheng, PY
Nefedova, Y
Miele, L
Osborne, BA
Gabrilovich, D
[J]. BLOOD, 2003, 102 (12) : 3980 - 3988
[8] Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors
Cozzio, A
Passegué, E
Ayton, PM
Karsunky, H
Cleary, ML
Weissman, IL
[J]. GENES & DEVELOPMENT, 2003, 17 (24) : 3029 - 3035
[9] Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation
de Guzman, CG
Warren, AJ
Zhang, Z
Gartland, L
Erickson, P
Drabkin, H
Hiebert, SW
Klug, CA
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (15) : 5506 - 5517
[10] TRB3:: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver
Du, KY
Herzig, S
Kulkarni, RN
Montminy, M
[J]. SCIENCE, 2003, 300 (5625) : 1574 - 1577

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