Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-7
pubmed:abstractText
Mitochondrial complex II is a tumor suppressor comprised of four subunits (SdhA, SdhB, SdhC, and SdhD). Mutations in any of these should disrupt complex II enzymatic activity, yet defects in SdhA produce bioenergetic deficiency while defects in SdhB, SdhC, or SdhD induce tumor formation. The mechanisms underlying these differences are not known. We show that the inhibition of distal subunits of complex II, either pharmacologically or via RNA interference of SdhB, increases normoxic reactive oxygen species (ROS) production, increases hypoxia-inducible factor alpha (HIF-alpha) stabilization in an ROS-dependent manner, and increases growth rates in vitro and in vivo without affecting hypoxia-mediated activation of HIF-alpha. Proximal pharmacologic inhibition or RNA interference of complex II at SdhA, however, does not increase normoxic ROS production or HIF-alpha stabilization and results in decreased growth rates in vitro and in vivo. Furthermore, the enhanced growth rates resulting from SdhB suppression are inhibited by the suppression of HIF-1alpha and/or HIF-2alpha, indicating that the mechanism of SdhB-induced tumor formation relies upon ROS production and subsequent HIF-alpha activation. Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10458603, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10588737, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10648801, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10657297, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10833514, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-10945599, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-11377966, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-11527963, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-11569921, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-11605159, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-11818553, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-12200425, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-12384970, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-12560550, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-12811540, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-12853322, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-13129931, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-14527321, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-14595761, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-14623340, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-14722062, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-14985369, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15122348, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15531530, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15572694, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15652751, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15665296, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15821583, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15862307, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15987702, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-15989954, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16054088, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16054089, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16098467, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16098468, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16103922, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16195397, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16333244, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16452228, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16516853, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16612574, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16628086, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-16781453, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-17376234, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-17562787, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-17636259, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-17785204, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-2983613, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-7550341, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-9716135, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-9751731, http://linkedlifedata.com/resource/pubmed/commentcorrection/17967865-9852050
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
718-31
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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