The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells
Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further suppor...
Gespeichert in:
| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2010-07, Vol.70 (13), p.5528-5538 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5538 |
|---|---|
| container_issue | 13 |
| container_start_page | 5528 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 70 |
| creator | JAGANI, Zainab WIEDERSCHAIN, Dmitri WARMUTH, Markus SELLERS, William R DORSCH, Marion LOO, Alice DAN HE MOSHER, Rebecca FORDJOUR, Paul MONAHAN, John MORRISSEY, Michael YAO, Yung-Mae LENGAUER, Christoph |
| description | Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim. |
| doi_str_mv | 10.1158/0008-5472.can-09-4229 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733627854</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>733627854</sourcerecordid><originalsourceid>FETCH-LOGICAL-c451t-96ff2d4b5359d4e2b0853b0060f89a96dfba1dabc5f8728800871d57059f12133</originalsourceid><addsrcrecordid>eNpFkMtKxDAUhoMoOo4-gpKNuKrm2iRLLToKMzoLdRvSNsFK2oxJi8zb2-Koq8OB7z-XD4AzjK4w5vIaISQzzgS5qkyXIZUxQtQemGFOZSYY4_tg9sccgeOUPsaWY8QPwRFBnKJckBl4e3m3cB38tgptCRcxDBu4jqG3TQdv2ybD8DHBu5Rs1zfGQxci7MfECH717zA4uBp832y8haut9aE1sLDepxNw4IxP9nRX5-D1_u6leMiWz4vH4maZVYzjPlO5c6RmJadc1cySEklOS4Ry5KQyKq9daXBtyoo7KYiU4z8C11wgrhwmmNI5uPyZu4nhc7Cp122TqvEC09kwJC0ozYmQnI0k_yGrGFKK1ulNbFoTtxojPRnVky092dLFzZNGSk9Gx9z5bsNQtrb-S_0qHIGLHWBSZbyLpqua9M8RJRjGOf0G_jN9Cw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733627854</pqid></control><display><type>article</type><title>The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>JAGANI, Zainab ; WIEDERSCHAIN, Dmitri ; WARMUTH, Markus ; SELLERS, William R ; DORSCH, Marion ; LOO, Alice ; DAN HE ; MOSHER, Rebecca ; FORDJOUR, Paul ; MONAHAN, John ; MORRISSEY, Michael ; YAO, Yung-Mae ; LENGAUER, Christoph</creator><creatorcontrib>JAGANI, Zainab ; WIEDERSCHAIN, Dmitri ; WARMUTH, Markus ; SELLERS, William R ; DORSCH, Marion ; LOO, Alice ; DAN HE ; MOSHER, Rebecca ; FORDJOUR, Paul ; MONAHAN, John ; MORRISSEY, Michael ; YAO, Yung-Mae ; LENGAUER, Christoph</creatorcontrib><description>Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-09-4229</identifier><identifier>PMID: 20530672</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Apoptosis - genetics ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Bcl-2-Like Protein 11 ; Biological and medical sciences ; Cell Growth Processes - genetics ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Hematologic and hematopoietic diseases ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Multiple Myeloma - genetics ; Multiple Myeloma - metabolism ; Multiple Myeloma - pathology ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Pharmacology. Drug treatments ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Transcription, Genetic ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2010-07, Vol.70 (13), p.5528-5538</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-96ff2d4b5359d4e2b0853b0060f89a96dfba1dabc5f8728800871d57059f12133</citedby><cites>FETCH-LOGICAL-c451t-96ff2d4b5359d4e2b0853b0060f89a96dfba1dabc5f8728800871d57059f12133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22974116$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20530672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JAGANI, Zainab</creatorcontrib><creatorcontrib>WIEDERSCHAIN, Dmitri</creatorcontrib><creatorcontrib>WARMUTH, Markus</creatorcontrib><creatorcontrib>SELLERS, William R</creatorcontrib><creatorcontrib>DORSCH, Marion</creatorcontrib><creatorcontrib>LOO, Alice</creatorcontrib><creatorcontrib>DAN HE</creatorcontrib><creatorcontrib>MOSHER, Rebecca</creatorcontrib><creatorcontrib>FORDJOUR, Paul</creatorcontrib><creatorcontrib>MONAHAN, John</creatorcontrib><creatorcontrib>MORRISSEY, Michael</creatorcontrib><creatorcontrib>YAO, Yung-Mae</creatorcontrib><creatorcontrib>LENGAUER, Christoph</creatorcontrib><title>The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Bcl-2-Like Protein 11</subject><subject>Biological and medical sciences</subject><subject>Cell Growth Processes - genetics</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - metabolism</subject><subject>Multiple Myeloma - pathology</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Polycomb Repressive Complex 1</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtKxDAUhoMoOo4-gpKNuKrm2iRLLToKMzoLdRvSNsFK2oxJi8zb2-Koq8OB7z-XD4AzjK4w5vIaISQzzgS5qkyXIZUxQtQemGFOZSYY4_tg9sccgeOUPsaWY8QPwRFBnKJckBl4e3m3cB38tgptCRcxDBu4jqG3TQdv2ybD8DHBu5Rs1zfGQxci7MfECH717zA4uBp832y8haut9aE1sLDepxNw4IxP9nRX5-D1_u6leMiWz4vH4maZVYzjPlO5c6RmJadc1cySEklOS4Ry5KQyKq9daXBtyoo7KYiU4z8C11wgrhwmmNI5uPyZu4nhc7Cp122TqvEC09kwJC0ozYmQnI0k_yGrGFKK1ulNbFoTtxojPRnVky092dLFzZNGSk9Gx9z5bsNQtrb-S_0qHIGLHWBSZbyLpqua9M8RJRjGOf0G_jN9Cw</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>JAGANI, Zainab</creator><creator>WIEDERSCHAIN, Dmitri</creator><creator>WARMUTH, Markus</creator><creator>SELLERS, William R</creator><creator>DORSCH, Marion</creator><creator>LOO, Alice</creator><creator>DAN HE</creator><creator>MOSHER, Rebecca</creator><creator>FORDJOUR, Paul</creator><creator>MONAHAN, John</creator><creator>MORRISSEY, Michael</creator><creator>YAO, Yung-Mae</creator><creator>LENGAUER, Christoph</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100701</creationdate><title>The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells</title><author>JAGANI, Zainab ; WIEDERSCHAIN, Dmitri ; WARMUTH, Markus ; SELLERS, William R ; DORSCH, Marion ; LOO, Alice ; DAN HE ; MOSHER, Rebecca ; FORDJOUR, Paul ; MONAHAN, John ; MORRISSEY, Michael ; YAO, Yung-Mae ; LENGAUER, Christoph</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-96ff2d4b5359d4e2b0853b0060f89a96dfba1dabc5f8728800871d57059f12133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Bcl-2-Like Protein 11</topic><topic>Biological and medical sciences</topic><topic>Cell Growth Processes - genetics</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - metabolism</topic><topic>Multiple Myeloma - pathology</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Polycomb Repressive Complex 1</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Transcription, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JAGANI, Zainab</creatorcontrib><creatorcontrib>WIEDERSCHAIN, Dmitri</creatorcontrib><creatorcontrib>WARMUTH, Markus</creatorcontrib><creatorcontrib>SELLERS, William R</creatorcontrib><creatorcontrib>DORSCH, Marion</creatorcontrib><creatorcontrib>LOO, Alice</creatorcontrib><creatorcontrib>DAN HE</creatorcontrib><creatorcontrib>MOSHER, Rebecca</creatorcontrib><creatorcontrib>FORDJOUR, Paul</creatorcontrib><creatorcontrib>MONAHAN, John</creatorcontrib><creatorcontrib>MORRISSEY, Michael</creatorcontrib><creatorcontrib>YAO, Yung-Mae</creatorcontrib><creatorcontrib>LENGAUER, Christoph</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JAGANI, Zainab</au><au>WIEDERSCHAIN, Dmitri</au><au>WARMUTH, Markus</au><au>SELLERS, William R</au><au>DORSCH, Marion</au><au>LOO, Alice</au><au>DAN HE</au><au>MOSHER, Rebecca</au><au>FORDJOUR, Paul</au><au>MONAHAN, John</au><au>MORRISSEY, Michael</au><au>YAO, Yung-Mae</au><au>LENGAUER, Christoph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>70</volume><issue>13</issue><spage>5528</spage><epage>5538</epage><pages>5528-5538</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>20530672</pmid><doi>10.1158/0008-5472.can-09-4229</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2010-07, Vol.70 (13), p.5528-5538 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733627854 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antineoplastic agents Apoptosis - genetics Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Bcl-2-Like Protein 11 Biological and medical sciences Cell Growth Processes - genetics Cell Line, Tumor Female Gene Expression Regulation, Neoplastic Hematologic and hematopoietic diseases Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred NOD Mice, SCID Multiple Myeloma - genetics Multiple Myeloma - metabolism Multiple Myeloma - pathology Nuclear Proteins - genetics Nuclear Proteins - metabolism Pharmacology. Drug treatments Polycomb Repressive Complex 1 Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism Transcription, Genetic Tumors |
| title | The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T12%3A13%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Polycomb%20Group%20Protein%20Bmi-1%20Is%20Essential%20for%20the%20Growth%20of%20Multiple%20Myeloma%20Cells&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=JAGANI,%20Zainab&rft.date=2010-07-01&rft.volume=70&rft.issue=13&rft.spage=5528&rft.epage=5538&rft.pages=5528-5538&rft.issn=0008-5472&rft.eissn=1538-7445&rft.coden=CNREA8&rft_id=info:doi/10.1158/0008-5472.can-09-4229&rft_dat=%3Cproquest_cross%3E733627854%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733627854&rft_id=info:pmid/20530672&rfr_iscdi=true |