Linked Life Data

16462766

Source:http://linkedlifedata.com/resource/pubmed/id/16462766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2006-6-15
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3565-75
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16462766-Animals, pubmed-meshheading:16462766-Antineoplastic Agents, Phytogenic, pubmed-meshheading:16462766-Apoptosis, pubmed-meshheading:16462766-Cell Line, Tumor, pubmed-meshheading:16462766-Cell Movement, pubmed-meshheading:16462766-Colonic Neoplasms, pubmed-meshheading:16462766-DNA-Binding Proteins, pubmed-meshheading:16462766-Drug Resistance, Neoplasm, pubmed-meshheading:16462766-Humans, pubmed-meshheading:16462766-Intestinal Mucosa, pubmed-meshheading:16462766-Oncogene Protein v-akt, pubmed-meshheading:16462766-Paclitaxel, pubmed-meshheading:16462766-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16462766-Proto-Oncogenes, pubmed-meshheading:16462766-Rats, pubmed-meshheading:16462766-Signal Transduction, pubmed-meshheading:16462766-Transcription Factors, pubmed-meshheading:16462766-Transcriptional Activation, pubmed-meshheading:16462766-Transforming Growth Factor beta
pubmed:year
2006
pubmed:articleTitle
Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT.
pubmed:affiliation
Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural