Abstract
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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins / pharmacology*
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CDC2-CDC28 Kinases*
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Carcinoma / metabolism*
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Carcinoma / pathology
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Cell Count
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Cell Cycle / drug effects
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Cell Cycle Proteins / metabolism*
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Cell Division / drug effects
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism*
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Dose-Response Relationship, Drug
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Flow Cytometry
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G1 Phase / drug effects
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Humans
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins*
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Retinoblastoma Protein / metabolism
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Thyroid Neoplasms / metabolism*
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Thyroid Neoplasms / pathology
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Transforming Growth Factor beta*
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
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Up-Regulation / drug effects
Substances
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BMP7 protein, human
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Transforming Growth Factor beta
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK4 protein, human
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CDK6 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6
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Cyclin-Dependent Kinases