BMI-1 promotes Ewing sarcoma tumorigenicity independent of CDKN2A repression

被引：114

作者：

Douglas, Dorothea ^{[1
]}

Hsu, Jessie Hao-Ru ^{[1
]}

Hung, Long ^{[1
]}

Cooper, Aaron ^{[1
]}

Abdueva, Diana ^{[2
]}

van Doorninck, John ^{[1
]}

Peng, Grace ^{[1
]}

Shimada, Hiro ^{[3
]}

Triche, Timothy J. ^{[2
,3
]}

Lawlor, Elizabeth R. ^{[1
,2
,3
]}

机构：

[1] Univ So Calif, Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA

[2] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA

[3] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

来源：

CANCER RESEARCH | 2008年 / 68卷 / 16期

关键词：

D O I：

10.1158/0008-5472.CAN-07-6152

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Deregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo. Moreover, we find that BMI-1 promotes the tumorigenicity of both p16 wild-type and p16-null cell lines, demonstrating that the mechanism of BMI-1 oncogenic function in ESFT is, at least in part, independent of CDKN2A repression. Expression profiling studies of ESFT cells following BMI-1 knockdown reveal that BMI-1 regulates the expression of hundreds of downstream target genes including, in particular, genes involved in both differentiation and development as well as cell-cell and cell-matrix adhesion. Gain and loss of function assays confirm that BMI-1 represses the expression of the adhesion-associated basement membrane protein nidogen 1. In addition, although BMI-1 promotes ESFT adhesion, nidogen 1 inhibits cellular adhesion in vitro. Together, these data support a pivotal role for BMI-1 ESFT pathogenesis and suggest that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways.

引用

页码：6507 / 6515

页数：9

共 51 条

[51] The EWS/FLI1 oncogenic transcription factor deregulates GLI1 [J].

Zwerner, J. P. ;

Joo, J. ;

Warner, K. L. ;

Christensen, L. ;

Hu-Lieskovan, S. ;

Triche, T. J. ;

May, W. A. .

ONCOGENE, 2008, 27 (23) :3282-3291

← 1 2 3 4 5 6 →