Document Detail

Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT.
MedLine Citation:
PMID:  16462766     Owner:  NLM     Status:  MEDLINE    
In hematopoietic cells the transforming potential of the ecotropic viral integration site 1 (Evi1) oncogene is thought to be dependent upon the ability to inhibit TGFbeta signaling. Although Evi1 has recently been implicated in certain epithelial cancers, the effects of Evi1 on transformation and TGFbeta signaling in epithelial cells are not completely understood. Herein, we have determined the effects of Evi1 on TGFbeta signaling in intestinal epithelial cells. Stable expression of Evi1 in non-transformed intestinal epithelial cells inhibited induction of some Smad3-dependent TGFbeta target genes, such as PAI1. However, TGFbeta-mediated induction of cellular adhesion signaling components such as integrin1 and paxillin was not inhibited by Evi1; nor did Evi1 inhibit TGFbeta-mediated epithelial to mesenchymal transition. Likewise, Evi1 did not inhibit TGFbeta-mediated downregulation of cyclin D1 or block TGFbeta-mediated growth inhibition. However, Evi1 did inhibit TGFbeta-mediated apoptosis by a process that involves phosphoinositide-3-kinase (PI3K) and its downstream effector AKT. The ability of Evi1 to suppress apoptosis is not restricted to TGFbeta-mediated cell death, since Evi1 also protects intestinal epithelial cells from taxol-mediated apoptosis. Evi1 is overexpressed in some human colon cancer cell lines, and overexpression is associated with amplification of the Evi1 gene. Knockdown of Evi1 by siRNA inhibited AKT phosphorylation in HT-29 human colon cancer cells and increased their sensitivity to taxol-mediated apoptosis. These data indicate that Evi1 functions as a survival gene in intestinal epithelial cells and colon cancer cells, activating PI3K/AKT and conveying resistance to both physiological and therapeutic apoptotic stimuli.
Y Liu; L Chen; T C Ko; A P Fields; E A Thompson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-02-06
Journal Detail:
Title:  Oncogene     Volume:  25     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-15     Completed Date:  2006-08-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3565-75     Citation Subset:  IM    
Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / physiology
Cell Line, Tumor
Cell Movement / physiology
Colonic Neoplasms / metabolism
DNA-Binding Proteins / metabolism*
Drug Resistance, Neoplasm / physiology*
Intestinal Mucosa / metabolism
Oncogene Protein v-akt / metabolism*
Paclitaxel / pharmacology*
Proto-Oncogenes / physiology*
Signal Transduction / physiology
Transcription Factors / metabolism*
Transcriptional Activation
Transforming Growth Factor beta / metabolism*
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/DNA-Binding Proteins; 0/Transcription Factors; 0/Transforming Growth Factor beta; 33069-62-4/Paclitaxel; EC 3-Kinase; EC Protein v-akt

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