Linked Life Data

19347030

Source:http://linkedlifedata.com/resource/pubmed/id/19347030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2009-5-7
pubmed:abstractText
Mammalian Stanniocalcin-1 (STC1) is a glycoprotein that has been implicated in various biological processes including angiogenesis. Aberrant STC1 expression has been reported in breast, ovarian and prostate cancers, but the significance of this is not well understood. Here, we report that oxidative stress caused a 40-fold increase in STC1 levels in mouse embryo fibroblasts (MEFs). STC1-/- MEFs were resistant to growth inhibition and cell death induced by H(2)O(2) or by 20% O(2) (which is hyperoxic for most mammalian cells); this is the first phenotype reported for STC1-null cells. STC1-/- cells had higher levels of activated MEK and ERK1/2 than their wild-type (WT) counterparts, and these levels were all reduced by stable expression of exogenous STC1 in STC1-/- cells. Furthermore, pharmacological inhibition by PD98059 or UO126 of MEK and therefore of ERK1/2 activation restored sensitivity of STC1-/- cells to oxidative stress. We also found that H(2)O(2)-induced STC1 expression in WT cells was abolished by inhibition of ERK1/2 activation. Thus, the ERK1/2 signaling pathway upregulates STC1 expression, which in turn downregulates the level of activated MEK and consequently ERK1/2 in a novel negative feedback loop. Therefore, STC1 expression downregulates prosurvival ERK1/2 signaling and reduces survival under conditions of oxidative stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1982-92
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress.
pubmed:affiliation
Cancer Research Unit, Children's Medical Research Institute, New South Wales, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't