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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
39
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pubmed:dateCreated |
2003-9-22
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pubmed:abstractText |
To study the role of IGF-I receptor signaling on cell cycle events we utilized MCF-7 breast cancer cells. IGF-I at physiological concentrations increased the level of p21CIP/WAF mRNA after 4has well as protein after 8hby 10- and 6-fold, respectively, in MCF-7 cells. This IGF-1 effect was reduced by 50% in MCF-7-derived cells (SX13), which exhibit a 50% reduction in IGF-1R expression, demonstrating that IGF-1 receptor activation was involved in this process. Preincubation with the ERK1/2 inhibitor U0126 significantly reduced the IGF-1 effect on the amount of p21CIP/WAF protein in MCF-7 cells. These results were confirmed by the expression of a dominant negative construct for MEK-1 suggesting that the increase of the abundance of p21CIP/WAF in response to IGF-1 occurs via the ERK1/2 mitogen-activated protein kinase pathway. Using an antisense strategy, we demonstrated that abolition of p21CIP/WAF expression decreased by 2-fold the IGF-1 effect on cell proliferation in MCF-7. This latter result is explained by a delay in G1 to S cell cycle progression due partly to a reduction in the activation of some components of cell cycle including the induction of cyclin D1 expression in response to IGF-1. MCF-7 cells transiently overexpressing p21 showed increased basal and IGF-I-induced thymidine incorporation. Taken together, these results define p21CIP/WAF as a positive regulator in the cell proliferation induced by IGF-1 in MCF-7 cells.
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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/CDK4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37256-64
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12867429-Breast Neoplasms,
pubmed-meshheading:12867429-Cell Division,
pubmed-meshheading:12867429-Cell Line, Tumor,
pubmed-meshheading:12867429-Cyclin D1,
pubmed-meshheading:12867429-Cyclin-Dependent Kinase 4,
pubmed-meshheading:12867429-Cyclin-Dependent Kinase 6,
pubmed-meshheading:12867429-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:12867429-Cyclin-Dependent Kinases,
pubmed-meshheading:12867429-Cyclins,
pubmed-meshheading:12867429-Female,
pubmed-meshheading:12867429-G1 Phase,
pubmed-meshheading:12867429-Humans,
pubmed-meshheading:12867429-Insulin-Like Growth Factor I,
pubmed-meshheading:12867429-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12867429-Phosphorylation,
pubmed-meshheading:12867429-Proto-Oncogene Proteins,
pubmed-meshheading:12867429-RNA, Antisense,
pubmed-meshheading:12867429-Retinoblastoma Protein
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pubmed:year |
2003
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pubmed:articleTitle |
The cyclin-dependent kinase inhibitor p21CIP/WAF is a positive regulator of insulin-like growth factor I-induced cell proliferation in MCF-7 human breast cancer cells.
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pubmed:affiliation |
Section on Molecular and Cellular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1758, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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