Source:http://linkedlifedata.com/resource/pubmed/id/16469805
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2006-4-17
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| pubmed:abstractText |
IGF binding protein (IGFBP)-3 inhibits cell growth and promotes apoptosis by sequestering free IGFs. In addition IGFBP-3 has IGF-independent, proapoptotic, antiproliferative effects on prostate cancer cells in vitro. Expression of the large T-antigen (Tag) under the long probasin promoter (LPB) in LPB-Tag mice results in prostate tumorigenesis. To investigate the IGF-dependent and IGF-independent effects of IGFBP-3 on prostate tumor growth, we crossed LPB-Tag mice with cytomegalovirus (CMVBP-3) and phosphoglycerate kinase (PGKBP-3) mice that overexpress IGFBP-3 under the cytomegalovirus promoter and the phosphoglycerate kinase promoter, respectively, and also I56G/L80G/L81G-mutant IGFBP-3 (PGKmBP-3) mice that express I56G/L80G/L81G-IGFBP-3, a mutant, that does not bind IGF-I but retains IGF-independent proapoptotic effects in vitro. Prostate tumor size and the steady-state level of p53 were attenuated in LPB-Tag/CMVBP-3 and LPB-Tag/PGKBP-3 mice, compared with LPB-Tag/wild-type (Wt) mice. A more marked effect was observed in LPB-Tag/CMVBP-3, compared with LPB-Tag/PGKBP-3, reflecting increased levels of transgene expression in CMVBP-3 prostate tissue. No attenuation of tumor growth was observed in LPB-Tag/PGKmBP-3 mice during the early tumor development, indicating that the inhibitory effects of IGFBP-3 were most likely IGF dependent during the initiation of tumorigenesis. At 15 wk of age, epidermal growth factor receptor expression was increased in LPB-Tag/Wt and LPB-Tag/PGKmBP-3 tissue, compared with LPB-Tag/PGKBP-3. IGF receptor was increased in all transgenic mice, but pAkt expression, a marker of downstream IGF-I action, was increased only in LPB-Tag/Wt and LPB-Tag/PGKmBP-3. After 15 wk of age, a marked reduction in tumor growth was apparent in LPB-Tag/PGKmBP-3 mice, indicating that the IGF-independent effects of IGFBP-3 may be important in inhibiting tumor progression.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoglycerate Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleases
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
147
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2112-21
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16469805-Animals,
pubmed-meshheading:16469805-Apoptosis,
pubmed-meshheading:16469805-Cell Proliferation,
pubmed-meshheading:16469805-Crosses, Genetic,
pubmed-meshheading:16469805-Cytomegalovirus,
pubmed-meshheading:16469805-Disease Progression,
pubmed-meshheading:16469805-Female,
pubmed-meshheading:16469805-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16469805-Genotype,
pubmed-meshheading:16469805-Immunoblotting,
pubmed-meshheading:16469805-Immunohistochemistry,
pubmed-meshheading:16469805-Insulin-Like Growth Factor Binding Protein 3,
pubmed-meshheading:16469805-Insulin-Like Growth Factor I,
pubmed-meshheading:16469805-Ligands,
pubmed-meshheading:16469805-Male,
pubmed-meshheading:16469805-Mice,
pubmed-meshheading:16469805-Mice, Transgenic,
pubmed-meshheading:16469805-Mutation,
pubmed-meshheading:16469805-Phenotype,
pubmed-meshheading:16469805-Phosphoglycerate Kinase,
pubmed-meshheading:16469805-Promoter Regions, Genetic,
pubmed-meshheading:16469805-Prostatic Neoplasms,
pubmed-meshheading:16469805-RNA,
pubmed-meshheading:16469805-RNA, Messenger,
pubmed-meshheading:16469805-Receptor, Epidermal Growth Factor,
pubmed-meshheading:16469805-Regression Analysis,
pubmed-meshheading:16469805-Ribonucleases,
pubmed-meshheading:16469805-Time Factors,
pubmed-meshheading:16469805-Transgenes,
pubmed-meshheading:16469805-Up-Regulation
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| pubmed:year |
2006
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| pubmed:articleTitle |
Insulin-like growth factor (IGF) binding protein-3 attenuates prostate tumor growth by IGF-dependent and IGF-independent mechanisms.
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| pubmed:affiliation |
Department of Physiology, University of Manitoba, Winnipeg, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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