BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1)
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...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2001-07, Vol.285 (3), p.773-781 |
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| creator | Franzén A Heldin, N E |
| description | 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. |
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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.</description><identifier>ISSN: 0006-291X</identifier><identifier>PMID: 11453659</identifier><language>eng</language><publisher>United States</publisher><subject>Bone Morphogenetic Protein 7 ; Bone Morphogenetic Proteins - pharmacology ; Carcinoma - metabolism ; Carcinoma - pathology ; CDC2-CDC28 Kinases ; 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 ; Thyroid Neoplasms - pathology ; Transforming Growth Factor beta ; Tumor Cells, Cultured ; Tumor Suppressor Proteins ; Up-Regulation - drug effects</subject><ispartof>Biochemical and biophysical research communications, 2001-07, Vol.285 (3), p.773-781</ispartof><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11453659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Franzén A</creatorcontrib><creatorcontrib>Heldin, N E</creatorcontrib><title>BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1)</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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.</description><subject>Bone Morphogenetic Protein 7</subject><subject>Bone Morphogenetic Proteins - pharmacology</subject><subject>Carcinoma - metabolism</subject><subject>Carcinoma - pathology</subject><subject>CDC2-CDC28 Kinases</subject><subject>Cell Count</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Cyclin-Dependent Kinase 2</subject><subject>Cyclin-Dependent Kinase 4</subject><subject>Cyclin-Dependent Kinase 6</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Cyclin-Dependent Kinases - metabolism</subject><subject>Cyclins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flow Cytometry</subject><subject>G1 Phase - drug effects</subject><subject>Humans</subject><subject>Phosphorylation - drug effects</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Transforming Growth Factor beta</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Suppressor Proteins</subject><subject>Up-Regulation - drug effects</subject><issn>0006-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEtLAzEcxHNQbK1-BclJ6mEhj26yOeqitVixhx68Lf_mgZF9mewK--1NtZ6Ggd8Mw5yhOSFEZEzR9xm6jPGTEEpXQl2gWdKci1zNETy87jKZ-daM2hqsbV1jPenaYgjBxgF3DkMLfQ1x8BoPH1PofOIgaN92DfwmIv72gHtGl-VmR-9SwCQnly9Hd4XOHdTRXp90gfZPj_vyOdu-rTfl_TbrKVdDdnCOgMjZqpBFwdRBiByMEkxLS3LKLLGaaaMV49bIFS-Mc5wXNBcFcYo6vkC3f7V96L7GtLxqfDyOg9Z2Y6wkUalNkgTenMDx0FhT9cE3EKbq_xP-A73tWes</recordid><startdate>20010720</startdate><enddate>20010720</enddate><creator>Franzén A</creator><creator>Heldin, N E</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010720</creationdate><title>BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1)</title><author>Franzén A ; Heldin, N E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p139t-bff0a6524878829b665ad962c7e0512e0ec2cdc923ed7438dff33815680f91f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Bone Morphogenetic Protein 7</topic><topic>Bone Morphogenetic Proteins - pharmacology</topic><topic>Carcinoma - metabolism</topic><topic>Carcinoma - pathology</topic><topic>CDC2-CDC28 Kinases</topic><topic>Cell Count</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Cyclin-Dependent Kinase 2</topic><topic>Cyclin-Dependent Kinase 4</topic><topic>Cyclin-Dependent Kinase 6</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Cyclin-Dependent Kinases - metabolism</topic><topic>Cyclins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flow Cytometry</topic><topic>G1 Phase - drug effects</topic><topic>Humans</topic><topic>Phosphorylation - drug effects</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins</topic><topic>Retinoblastoma Protein - metabolism</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Transforming Growth Factor beta</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Suppressor Proteins</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Franzén A</creatorcontrib><creatorcontrib>Heldin, N E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Franzén A</au><au>Heldin, N E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1)</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-07-20</date><risdate>2001</risdate><volume>285</volume><issue>3</issue><spage>773</spage><epage>781</epage><pages>773-781</pages><issn>0006-291X</issn><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.</abstract><cop>United States</cop><pmid>11453659</pmid><tpages>9</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Bone Morphogenetic Protein 7 Bone Morphogenetic Proteins - pharmacology Carcinoma - metabolism Carcinoma - pathology CDC2-CDC28 Kinases 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 Thyroid Neoplasms - pathology Transforming Growth Factor beta Tumor Cells, Cultured Tumor Suppressor Proteins Up-Regulation - drug effects |
| title | BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1) |
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