Linked Life Data

17260022

Source:http://linkedlifedata.com/resource/pubmed/id/17260022

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2007-6-21
pubmed:abstractText
The paired/homeodomain transcription factor Pax4 is essential for islet beta-cell generation during pancreas development and their survival in adulthood. High Pax4 expression was reported in human insulinomas indicating that deregulation of the gene may be associated with tumorigenesis. We report that rat insulinoma INS-1E cells express 25-fold higher Pax4 mRNA levels than rat islets. In contrast to primary beta-cells, activin A but not betacellulin or glucose induced Pax4 mRNA levels indicating dissociation of Pax4 expression from insulinoma cell proliferation. Short hairpin RNA adenoviral constructs targeted to the paired domain or homeodomain (viPax4PD and viPax4HD) were generated. Pax4 mRNA levels were lowered by 73 and 50% in cells expressing either viPax4PD or viPax4HD. Transcript levels of the Pax4 target gene bcl-xl were reduced by 53 and 47%, whereas Pax6 and Pdx1 mRNA levels were unchanged. viPax4PD-infected cells displayed a twofold increase in spontaneous apoptosis and were more susceptible to cytokine-induced cell death. In contrast, proliferation was unaltered. RNA interference-mediated repression of insulin had no adverse effects on either Pax4 or Pdx1 expression as well as on cell replication or apoptosis. These results indicate that Pax4 is redundant for proliferation of insulinoma cells, whereas it is essential for survival through upregulation of the antiapoptotic gene bcl-xl.
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
21
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4261-71
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells.
pubmed:affiliation
Department of Cell Physiology and Metabolism, University Medical Center, Geneva 4, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't