Linked Life Data

19960406

Source:http://linkedlifedata.com/resource/pubmed/id/19960406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-9
pubmed:abstractText
Insulin-like growth factor binding protein (IGFBP)-3 has been shown to potently inhibit proliferation of various cell types in an insulin-like growth factor (IGF)-independent manner. We have previously shown that IGFBP-3 induces apoptosis in an IGF-independent manner through the activation of caspases involved in a death receptor-mediated pathway in MCF-7 human breast cancer cells. In the present study, we present further evidence that IGFBP-3 inhibits cell proliferation through the induction of cell cycle arrest in the same cell line. Induction of IGFBP-3 in MCF-7 cells inhibited cell proliferation whereas presence of small interfering RNA against IGFBP-3 abolished cell inhibitory effect of IGFBP-3, suggesting that the observed growth inhibition is specific. Flow cytometry analysis showed that induced expression of IGFBP-3 led to an arrest of the cell cycle in G1-S phase. Western immunoblot analysis showed a significant decrease in the levels of the cell cycle-regulated proteins such as cyclin D1, cyclin D3, cyclin E, cyclin A, cyclin-dependent kinase (CDK) 2, CDK4, retinoblastoma protein (pRB), and phosph-pRB, suggesting a possible mechanism for cell cycle arrest by IGFBP-3. Northern blot analysis and real-time quantitative PCR demonstrated a significant decrease in gene expression of cyclin D1. Additional phosphorylation assay showed that IGFBP-3 decreased the phosphorylation activity of CDK2 and CDK4. These results show that cellular production of IGFBP-3 leads to G1 cell cycle arrest with inhibition of CDK2 and CDK4. Taken together, IGFBP-3 exerts its growth inhibitory action through not only induction of apoptosis but also the G1 cell cycle arrest in human breast cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDK4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Ecdysterone, http://linkedlifedata.com/resource/pubmed/chemical/IGFBP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding..., http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/ponasterone A
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1439-4286
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-72
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Insulin-like growth factor binding protein-3 induces G1 cell cycle arrest with inhibition of cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells.
pubmed:affiliation
Department of Pediatrics, Yonsei University, Seoul, Korea. kimho@yuhs.ac
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't