Source:http://linkedlifedata.com/resource/pubmed/id/21335545
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2011-3-16
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| pubmed:abstractText |
Oncogenic activation of K-ras occurs commonly in non-small cell lung cancer (NSCLC), but strategies to therapeutically target this pathway have been challenging to develop. Information about downstream effectors of K-ras remains incomplete, and tractable targets are yet to be defined. In this study, we investigated the role of protein kinase C ? (PKC?) in K-ras-dependent lung tumorigenesis by using a mouse carcinogen model and human NSCLC cells. The incidence of urethane-induced lung tumors was decreased by 69% in PKC?-deficient knockout (?KO) mice compared with wild-type (?WT) mice. ?KO tumors are smaller and showed reduced proliferation. DNA sequencing indicated that all ?WT tumors had activating mutations in KRAS, whereas only 69% of ?KO tumors did, suggesting that PKC? acts as a tumor promoter downstream of oncogenic K-ras while acting as a tumor suppressor in other oncogenic contexts. Similar results were obtained in a panel of NSCLC cell lines with oncogenic K-ras but which differ in their dependence on K-ras for survival. RNA interference-mediated attenuation of PKC? inhibited anchorage-independent growth, invasion, migration, and tumorigenesis in K-ras-dependent cells. These effects were associated with suppression of mitogen-activated protein kinase pathway activation. In contrast, PKC? attenuation enhanced anchorage-independent growth, invasion, and migration in NSCLC cells that were either K-ras-independent or that had WT KRAS. Unexpectedly, our studies indicate that the function of PKC? in tumor cells depends on a specific oncogenic context, as loss of PKC? in NSCLC cells suppressed transformed growth only in cells dependent on oncogenic K-ras for proliferation and survival.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1538-7445
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| pubmed:author | |
| pubmed:copyrightInfo |
©2011 AACR.
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| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
71
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2087-97
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| pubmed:meshHeading |
pubmed-meshheading:21335545-Animals,
pubmed-meshheading:21335545-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:21335545-Cell Line,
pubmed-meshheading:21335545-Cell Line, Tumor,
pubmed-meshheading:21335545-Cell Movement,
pubmed-meshheading:21335545-Cell Proliferation,
pubmed-meshheading:21335545-Cell Survival,
pubmed-meshheading:21335545-Enzyme Activation,
pubmed-meshheading:21335545-Female,
pubmed-meshheading:21335545-Humans,
pubmed-meshheading:21335545-Immunoblotting,
pubmed-meshheading:21335545-Lung Neoplasms,
pubmed-meshheading:21335545-Male,
pubmed-meshheading:21335545-Mice,
pubmed-meshheading:21335545-Mice, Inbred C57BL,
pubmed-meshheading:21335545-Mice, Knockout,
pubmed-meshheading:21335545-Mice, Nude,
pubmed-meshheading:21335545-Mitogen-Activated Protein Kinases,
pubmed-meshheading:21335545-Mutation,
pubmed-meshheading:21335545-Protein Kinase C-delta,
pubmed-meshheading:21335545-RNA Interference,
pubmed-meshheading:21335545-Tumor Burden,
pubmed-meshheading:21335545-Urethane,
pubmed-meshheading:21335545-ras Proteins
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| pubmed:year |
2011
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| pubmed:articleTitle |
Protein kinase C ? is a downstream effector of oncogenic K-ras in lung tumors.
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| pubmed:affiliation |
Program in Cancer Biology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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