Linked Life Data

12635656

Source:http://linkedlifedata.com/resource/pubmed/id/12635656

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-3-14
pubmed:abstractText
Nitric oxide (NO) plays a key role in attenuation of tumor growth by activated macrophages that generate large amount of cytotoxic/cytostatic free radicals. However, some tumor cells may survive from NO cytotoxicity and continue to proliferate to malignant tumors. Since a protooncogene product Ras was shown to be activated by NO, this study investigated the involvement of Ras in the cell survival in response to NO cytotoxicity in pheochromocytoma (PC12) cells. Treatment with Ras inhibitor or constitutive expression of dominant negative Ras markedly increased NO-induced cell death. NO-resistant PC12 cells (PC12-NO-R) exhibited higher steady state Ras activity than the parental PC12 cells. Inducible expression using tetracycline-on (Tet-on) system of Ras mutants (dominant negative Ras or dominant active Ras) demonstrated that blockade of Ras activity increased NO-induced cell death whereas enhancement of Ras activity attenuated NO-induced cell death. Furthermore, inducible expression of NO-insensitive mutant Ras selectively increased cellular vulnerability to NO but not to ROS. NO, Ras inhibitor and extracellular signal-regulated kinase (Erk) blocker synergistically increased cell death. These observations suggest that Ras activity may be a critical factor for survival response of tumor cells to NO toxicity and pharmacological agents affecting Ras activity may enhance efficacy of NO-mediated tumor therapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0167-594X
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-107
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Involvement of Ras in survival responsiveness to nitric oxide toxicity in pheochromocytoma cells.
pubmed:affiliation
Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't