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Status |
Public on Jul 18, 2008 |
Title |
BMI-1 promotes Ewing sarcoma tumorigenicity independent of CDKN2a-repression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Over-expression of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we investigate the role of BMI-1 as a functional oncogene in the Ewing’s Sarcoma Family of Tumors (ESFT), a highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by the majority of primary ESFT and ESFT cell lines. However, in contrast to previous reports in other human cancer cell types, knockdown of BMI-1 in ESFT cell lines has no effect on cell survival. Instead, gain and loss of function studies in vitro and in vivo demonstrate that BMI-1 promotes the anchorage independent growth and tumorigenicity of ESFT. Importantly, we also find that modulation of BMI-1 alters the tumorigenicity of both p16-wild type and p16-null cell lines and that BMI-1-mediated effects on growth promotion are independent of CDKN2a repression. Gene expression profiling of ESFT cells following BMI-1 modulation reveals novel downstream effectors of BMI-1 function including key developmental, cell:cell and cell:matrix adhesion pathways. These data support a central role for BMI-1 in the pathogenesis of ESFT and reveal that p16-independent functions of BMI-1 are largely responsible for its oncogenic function in this tumor family.
Keywords: Modification of BMI-1 expression in ESFT cell lines
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Overall design |
6 samples, 2 conditions, 3 replicates per condition
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Contributor(s) |
Lawlor ER |
Citation(s) |
18701473 |
Submission date |
Jul 10, 2008 |
Last update date |
Feb 18, 2019 |
Contact name |
Elizabeth R Lawlor |
E-mail(s) |
elawlor@umich.edu
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Organization name |
University of Michigan
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Street address |
1600 Huron Parkway, NCRC Bldg 520
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City |
Ann Arbor |
State/province |
MI |
ZIP/Postal code |
48109-2800 |
Country |
USA |
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Platforms (1) |
GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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Samples (6)
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Relations |
BioProject |
PRJNA113399 |
Supplementary file |
Size |
Download |
File type/resource |
GSE12064_RAW.tar |
117.4 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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