Document Detail


BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1).
MedLine Citation:
PMID:  11453659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present study was to investigate the effect of bone morphogenetic protein (BMP-7) on thyroid carcinoma cell growth. Addition of BMP-7 inhibited the proliferation of four out of six human anaplastic thyroid carcinoma cell lines, observed as decreased incorporation of (3)H-thymidine and decreased cell number. The growth inhibitory effect was cell density-dependent; sparse cells were inhibited by BMP-7 whereas dense cells were not. Cell cycle analysis by flow cytometry showed an increased fraction of cells in the G1-phase and subsequent decrease in both S- and G2/M-phase after BMP-7 stimulation. Furthermore, BMP-7 caused an upregulation of the cyclin-dependent kinase inhibitors (CDKIs) p21 and p27, decreased activity of Cdk2 and Cdk6, and hypophosphorylation of the retinoblastoma protein (pRb). These findings suggest a growth inhibitory effect of BMP-7 on anaplastic thyroid carcinoma cells by inhibition of Cdk activity shifting the Rb protein to the hypophosphorylated state.
Authors:
Franzén A; N E Heldin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  285     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-16     Completed Date:  2001-08-16     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  773-81     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Asa.Franzen@genpat.uu.se
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MeSH Terms
Descriptor/Qualifier:
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins / pharmacology*
CDC2-CDC28 Kinases*
Carcinoma / metabolism*,  pathology
Cell Count
Cell Cycle / drug effects
Cell Cycle Proteins / metabolism*
Cell Division / drug effects
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / metabolism
Cyclins / metabolism*
Dose-Response Relationship, Drug
Flow Cytometry
G1 Phase / drug effects
Humans
Phosphorylation / drug effects
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins*
Retinoblastoma Protein / metabolism
Thyroid Neoplasms / metabolism*,  pathology
Transforming Growth Factor beta*
Tumor Cells, Cultured
Tumor Suppressor Proteins*
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/BMP7 protein, human; 0/Bone Morphogenetic Protein 7; 0/Bone Morphogenetic Proteins; 0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Transforming Growth Factor beta; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/CDK6 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6; EC 2.7.11.22/Cyclin-Dependent Kinases

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