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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-6-24
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pubmed:abstractText |
SKP2, an F-box protein constituting the substrate recognition subunit of the SCF(SKP2) ubiquitin ligase complex, is implicated in ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27(KIP1). Our earlier studies revealed SKP2 as a target gene within the 5p13 amplicon that is often seen in small-cell lung cancers. In the present study we examined amplification status and expression levels of SKP2 in non-small-cell lung cancer (NSCLC) and investigated its clinicopathological significance in this type of tumor because amplification of DNA at 5p13 is observed frequently in NSCLCs as well as in small-cell lung cancers. SKP2 exhibited amplification in 5 (20%) of 25 cell lines derived from NSCLC, and the transcript was overexpressed in 11 (44%) of the 25 lines. Moreover, expression of SKP2 was up-regulated significantly in 60 primary NSCLC tumors as compared to nontumorous lung tissues (P < 0.0001). Elevated expression of SKP2 correlated significantly with positive lymph node metastasis (P = 0.007), with stage II or higher of the international TNM classification (P = 0.014), with poor or moderate differentiation (P < 0.001), and with the presence of squamous cell carcinoma (P = 0.037). Reduction of SKP2 expression by transfection of an anti-sense oligonucleotide inhibited invasion and migration of NSCLC cells in culture. Our results suggest that SKP2 may be involved in progression of NSCLC, and that targeting this molecule could represent a promising therapeutic option.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-10200246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-10338207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-10559916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-10559918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-10753747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11226270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11250155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11309491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11335900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11585732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-11943729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12029633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12097295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12107105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12208864,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12362270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12429629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12579266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12586812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12670908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-12824902,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-14707456,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-7553852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9187106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9192802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9472113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9591638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9616126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215173-9736735
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
175-80
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15215173-Blotting, Western,
pubmed-meshheading:15215173-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:15215173-Cell Line, Tumor,
pubmed-meshheading:15215173-Cell Movement,
pubmed-meshheading:15215173-Cell Survival,
pubmed-meshheading:15215173-Collagen,
pubmed-meshheading:15215173-Drug Combinations,
pubmed-meshheading:15215173-Gene Amplification,
pubmed-meshheading:15215173-Gene Expression,
pubmed-meshheading:15215173-Humans,
pubmed-meshheading:15215173-In Situ Hybridization, Fluorescence,
pubmed-meshheading:15215173-Laminin,
pubmed-meshheading:15215173-Lung Neoplasms,
pubmed-meshheading:15215173-Lymph Nodes,
pubmed-meshheading:15215173-Neoplasm Metastasis,
pubmed-meshheading:15215173-Neoplasm Staging,
pubmed-meshheading:15215173-Oligonucleotides, Antisense,
pubmed-meshheading:15215173-Polymerase Chain Reaction,
pubmed-meshheading:15215173-Proteoglycans,
pubmed-meshheading:15215173-S-Phase Kinase-Associated Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
Amplification and overexpression of SKP2 are associated with metastasis of non-small-cell lung cancers to lymph nodes.
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pubmed:affiliation |
Department of Molecular Cytogenetics, Graduate School of Biomedical Science, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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