Linked Life Data

20840848

Source:http://linkedlifedata.com/resource/pubmed/id/20840848

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-11-15
pubmed:abstractText
The molecular pathogenesis of hepatocellular carcinoma is well-studied but not completely understood. We utilized a microcell-hybrid model of tumor suppression in rat liver tumor cells to facilitate the identification of liver tumor suppressor genes located on human chromosome 11. These investigations confirmed a liver tumor suppressor locus at human 11p11.2, identified Wt1 as a potential effector of 11p11.2-mediated tumor suppression, and subsequently identified human SYT13 as a strong candidate for the 11p11.2 liver tumor suppressor gene. In the studies presented here, we introduced SYT13 into the GN6TF rat liver tumor cell line to characterize a functional role for SYT13 in this model system. Transfected clones expressing an SDS-resistant dimer form of the SYT13 protein displayed induction of Wt1 gene expression and a significant attenuation of the neoplastic phenotype exhibited by the parental tumor cell line. Saturation densities and anchorage-independent growth of SYT13 dimer-positive cell lines were reduced in vitro, and tumorigenicity was significantly decreased or ablated in syngeneic host rats in vivo. In addition, restoration of the contact-inhibited, epithelioid morphology observed in normal liver epithelial cells accompanied ectopic expression of the SYT13 protein dimer, suggesting that SYT13 may be mediating an epithelial differentiation coordinate with tumor suppression in these cells. Accordingly, the expression of E-cadherin (Cdh1) mRNA was increased >100-fold in SYT13-dimer-positive cell lines and the Cdh1 transcriptional repressor Snail was decreased >3-fold in these cells compared to the parental tumor cells. These studies combine to suggest that SYT13 is a liver tumor suppressor gene and that its function may be mediated through pathways implicated in mesenchymal to epithelial transition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-0945
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-16
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Exogenous expression of synaptotagmin XIII suppresses the neoplastic phenotype of a rat liver tumor cell line through molecular pathways related to mesenchymal to epithelial transition.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Program in Translational Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. jjahn@amgen.com
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural