Source:http://linkedlifedata.com/resource/pubmed/id/11212247
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-2-9
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| pubmed:abstractText |
Little is known about the status of the mitogen-activating protein kinase pathways in lung cancer. One of the key molecules taking part in these pathways is the product of the c-mos proto-oncogene, which plays an important role in oocyte maturation. In vitro investigations in somatic cells have shown that c-mos expression has opposing effects on the cell cycle, which suggests that this proto-oncogene may represent an important determinant of aberrant cell function (genomic instability and altered kinetics). A recent study suggests that these effects may be p53 dependent. In view of the apparent link between c-mos and p53, we investigated in a series of 56 non-small cell lung carcinomas: a) the status of c-mos; b) its relationship to genomic instability (aneuploidy) and two kinetic parameters of the tumors, proliferation and apoptotic indexes (AI); and c) its association with p53 alterations and their concomitant relationship with the above parameters. We found c-mos overexpression in 27% of the tumors. Expression was higher in stages II/III (34%) than in stage I (17%; P = 0.018). Complete concordance was observed between c-mos overexpression and elevated c-mos mRNA levels. Because c-mos gene amplification was not detected, its deregulated expression may be attributable to increased transcription. Of the c-mos positive [c-mos(P)] cases, 77% were associated with aneuploidy. Sequencing showed two silent mutations and one missense (R-->L) at codon 22, located in a region critical for c-mos stability. In contrast to the findings of some in vitro studies, c-mos(P) tumors had a lower mean AI score than the c-mos negative [c-mos(N)] tumors had, implying that induction of apoptosis may have been defective. Indeed, 86% of the tumors overexpressing c-mos showed p53 alterations. The carcinomas with concomitant alterations of c-mos and p53 [c-mos(P)/p53 positive] had significantly lower AI values (P < 0.001) and were more frequently associated with aneuploidy (P = 0.015) than the c-mos(N)/p53 negative tumors but not the c-mos(N)/p53 positive tumors, which suggests that p53 status is the main determinant of ploidy status and apoptosis in our series. This finding also strengthens the concept that wild-type p53 plays a "safeguard" role in preventing oncogene-mediated activation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mos,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0008-5472
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| pubmed:author |
pubmed-author:AsimacopoulosP JPJ,
pubmed-author:AthanasiouAA,
pubmed-author:FieldJ KJK,
pubmed-author:FoukasPP,
pubmed-author:GorgoulisV GVG,
pubmed-author:IkonomopoulosJJ,
pubmed-author:KastrinakisNN,
pubmed-author:KittasCC,
pubmed-author:KletsasDD,
pubmed-author:KokotasSS,
pubmed-author:KotsinasAA,
pubmed-author:LiloglouTT,
pubmed-author:MariatosGG,
pubmed-author:ZacharatosPP,
pubmed-author:ZoumpourlisVV
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| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
61
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
538-49
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11212247-Aged,
pubmed-meshheading:11212247-Aneuploidy,
pubmed-meshheading:11212247-Apoptosis,
pubmed-meshheading:11212247-Base Sequence,
pubmed-meshheading:11212247-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:11212247-Cell Division,
pubmed-meshheading:11212247-DNA, Neoplasm,
pubmed-meshheading:11212247-DNA Mutational Analysis,
pubmed-meshheading:11212247-Female,
pubmed-meshheading:11212247-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11212247-Humans,
pubmed-meshheading:11212247-Immunohistochemistry,
pubmed-meshheading:11212247-Lung Neoplasms,
pubmed-meshheading:11212247-Male,
pubmed-meshheading:11212247-Middle Aged,
pubmed-meshheading:11212247-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11212247-Mutation,
pubmed-meshheading:11212247-Neoplasm Staging,
pubmed-meshheading:11212247-Phosphorylation,
pubmed-meshheading:11212247-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:11212247-Proto-Oncogene Proteins c-mos,
pubmed-meshheading:11212247-RNA, Messenger,
pubmed-meshheading:11212247-Survival Analysis,
pubmed-meshheading:11212247-Tumor Suppressor Protein p53
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| pubmed:year |
2001
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| pubmed:articleTitle |
Deregulated expression of c-mos in non-small cell lung carcinomas: relationship with p53 status, genomic instability, and tumor kinetics.
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| pubmed:affiliation |
Department of Histology and Embryology, School of Medicine, University of Athens, Greece. histoclub@ath.forthnet.gr
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| pubmed:publicationType |
Journal Article
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