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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 |
2005-6-8
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pubmed:abstractText |
The cyclin-dependent kinase inhibitor p21cip1/waf1 negatively regulates the progression of cell cycle and the potential usefulness of p21cip1/waf1 gene is proposed in gene therapy. However, studies have demonstrated a protective role of p21cip1/waf1 against apoptosis and little is known about effects of ectopic expression of p21cip1/waf1 on differentiation of colon cancer cells. In the present study, we found diffuse p21cip1/waf1 expression in only a few clinical samples of colorectal cancer with wild-type p53 gene. To explore the role of p21cip1/waf1 in cell growth, apoptosis and differentiation, we constitutively overexpressed p21cip1/waf1 in HT29 colon carcinoma cells. Ectopic overexpression of p21cip1/waf1 was associated with inhibition of CDK2-associated kinase activity, indicating the functionality of the introduced p21cip1/waf1 gene. Overexpression of p21cip1/waf1 caused an appreciable growth inhibition in monolayer and soft agar cultures and it significantly reduced sodium butyrate- but not 5-fluorouracil-induced apoptosis. p21cip1/waf1 overexpressing cells exhibited marked decrease of intestinal differentiation when assayed with intestinal alkaline phosphatase. Our findings suggest that introduction of p21cip1/waf1 gene into colon cancer cells may be useful for inhibiting cell growth but caution should be taken regarding the increased resistance to certain apoptosis-inducing agents and dysregulation of endogenous p21cip1/waf1-mediated differentiation process.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Agar,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Butyric Acids,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Isobutyric Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/isobutyric acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1019-6439
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pubmed:author |
pubmed-author:DamdinsurenBazarragchaaB,
pubmed-author:HayashiTaroT,
pubmed-author:IkedaKimimasaK,
pubmed-author:IkedaMasatakaM,
pubmed-author:IzawaHikaruH,
pubmed-author:KitaniKotaroK,
pubmed-author:MondenMoritoM,
pubmed-author:MondenTakushiT,
pubmed-author:OhueMasayukiM,
pubmed-author:SekiYosukeY,
pubmed-author:SekimotoMitsuguM,
pubmed-author:SuzukiReiR,
pubmed-author:TakemasaIchiroI,
pubmed-author:TsujieMasakiM,
pubmed-author:YamamotoHirofumiH
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pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
69-76
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15942645-Agar,
pubmed-meshheading:15942645-Alkaline Phosphatase,
pubmed-meshheading:15942645-Apoptosis,
pubmed-meshheading:15942645-Blotting, Western,
pubmed-meshheading:15942645-Butyric Acids,
pubmed-meshheading:15942645-Carcinoma,
pubmed-meshheading:15942645-Cell Cycle Proteins,
pubmed-meshheading:15942645-Cell Differentiation,
pubmed-meshheading:15942645-Cell Line, Tumor,
pubmed-meshheading:15942645-Cell Proliferation,
pubmed-meshheading:15942645-Colonic Neoplasms,
pubmed-meshheading:15942645-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15942645-DNA Mutational Analysis,
pubmed-meshheading:15942645-Flow Cytometry,
pubmed-meshheading:15942645-Fluorouracil,
pubmed-meshheading:15942645-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15942645-Humans,
pubmed-meshheading:15942645-Inhibitory Concentration 50,
pubmed-meshheading:15942645-Isobutyric Acids,
pubmed-meshheading:15942645-Mutation,
pubmed-meshheading:15942645-Polymerase Chain Reaction,
pubmed-meshheading:15942645-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:15942645-Time Factors,
pubmed-meshheading:15942645-Tumor Suppressor Protein p53
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pubmed:year |
2005
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pubmed:articleTitle |
Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells.
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pubmed:affiliation |
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Japan.
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pubmed:publicationType |
Journal Article
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