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PMID: 12748291 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins.

Molecular and cellular biology ·Vol. 23 ·No. 11 ·2003-06-00 ·Pages 3897-908

Deneen B, Welford SM, Ho T, Hernandez F, Kurland I, Denny CT

Abstract

Despite significant structural diversity, present evidence suggests that EWS/ETS fusion proteins promote oncogenesis by transcriptionally modulating a common set of target genes. In order to identify these genes, microarray expression analyses were performed on NIH 3T3 polyclonal populations expressing one of three EWS/ETS fusion genes. The majority of these genes can be grouped into seven functional categories, including cellular metabolism and signal transduction. The biologic significance of these target genes was pursued. The effects of modulating genes involved in metabolism were assessed by flux studies and demonstrated shifts in glucose utilization and lactate production as a result of EWS/FLI1 expression. The proto-oncogene coding for serine/threonine kinase PIM3 was found to one of several genes encoding signal transduction proteins that were up-regulated by EWS/ETS fusions. PIM3 was found to be expressed in a panel of human Ewing's family tumor cell lines. Forced expression of PIM3 promoted anchorage-independent growth. Coexpression of a kinase-deficient PIM3 mutant attenuated EWS/FLI1-mediated NIH 3T3 tumorigenesis in immunodeficent mice.

MeSH Terms
3T3 Cells Animals Cell Adhesion/physiology Cell Division/physiology Cell Line Cell Transplantation Gene Expression Profiling Gene Expression Regulation Humans Mice Neoplasms/genetics,metabolism Oligonucleotide Array Sequence Analysis Protein Serine-Threonine Kinases/genetics,metabolism Proto-Oncogene Mas Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-ets RNA-Binding Protein EWS/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Survival Rate Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets RNA-Binding Protein EWS Recombinant Fusion Proteins Transcription Factors Protein Serine-Threonine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Deneen Benjamin
Molecular Biology Institute, University of California-Los Angeles, Los Angeles, California 90095, USA.
Welford Scott M
Ho Thu
Hernandez Felicia
Kurland Irwin
Denny Christopher T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.11.3897-3908.2003
Published
2003-06-00
Pages
3897-908
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC155223
Subset
IM
Grants
NCI NIH HHS · R01 CA087771 · United States
NCI NIH HHS · CA87771 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.11.3897-3908.2003 PMC Full Text View journal details
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