Loading…
Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma
Abstract Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathw...
Saved in:
| Published in: | Leukemia & lymphoma 2012-08, Vol.53 (8), p.1577-1585 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3 |
| container_end_page | 1585 |
| container_issue | 8 |
| container_start_page | 1577 |
| container_title | Leukemia & lymphoma |
| container_volume | 53 |
| creator | Thoennissen, Nils H. Thoennissen, Gabriela B. Abbassi, Sam Nabavi-Nouis, Shayan Sauer, Tim Doan, Ngan B. Gery, Sigal Müller-Tidow, Carsten Said, Jonathan W. Koeffler, H. Phillip |
| description | Abstract
Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathway in diffuse large B-cell lymphoma (DLBCL), one of the commonest types of mature B-cell lymphoma. Expression analysis of human B-cell lymphoma samples including DLBCL (n = 50), mantle cell (n = 21), follicular (n = 25) and Burkitt (n = 18) lymphoma revealed markedly down-regulated CEBPA and PER2 mRNA levels exclusively in DLBCL samples compared to control lymphatic tissue. We demonstrated direct regulation of the circadian core clock gene PER2 by C/EBPalpha in the pro-B cell line Ba/F3, and forced expression of PER2 resulted in decreased proliferation, G0/G1 cell cycle arrest and increased rates of apoptosis. Interestingly, treatment of human DLBCL cell lines with the histone deacetylase-inhibitor suberoylanilide hydroxamic acid (SAHA) significantly increased the expression of C/EBPalpha and Per2, accompanied by cell growth inhibition; in contrast, siRNA knockdown of CEBPA reduced the anti-proliferative effect of SAHA treatment. Our results show for the first time that C/EBPalpha with its associated direct core clock gene target, PER2, are highly deregulated in DLBCL, suggesting an important tumor suppressive pathway in the pathogenesis of this lymphoma entity. |
| doi_str_mv | 10.3109/10428194.2012.658792 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_infor</sourceid><recordid>TN_cdi_proquest_miscellaneous_1027371376</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1027371376</sourcerecordid><originalsourceid>FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhSMEoqXwBgh5ySZTx_lzNkVlVH6kSiA0rK0b-zpxcezBcajmlXhKHE1b0U1XtuRzzj3XX5a9LeimLGh3XtCK8aKrNowWbNPUvO3Ys-y0oKzLWUXL5-u9YvmqOclezfMNpbTuGvYyO2GMNbRoitPs7y6Am2Uw-2i8Ixpk9IFst5eXu3N0IziJIe-NU8YNZB98ROMI2P0IBJwiyRiNBEukCRKUAUek9fIXUf7WzTEgTCRCGDCSAR2S71c_GIGAZDTDaA9EYcBhsRBRkRSsjNbLjMSuFvIxl2gtsYdpP_oJXmcvNNgZ39ydZ9nPT1e77Zf8-tvnr9vL61zWvI65lJ3uQCms2rLlPUesCs04bXrQvFdayVZK4NByzbCGWvFWIvK6rJSUquzLs-zimLtf-gmVRBcDWLEPZoJwEB6MePzizCgG_0eUvEn_zlPA-7uA4H8vOEcxmXldBRz6ZRYJUapWlG2TpNVRKoOf54D6YUxBxYpZ3GMWK2ZxxJxs7_6v-GC655oEH44C47QPE9z6YJWIcLA-6ERcmnmNf3LExaOEEcHGUSZ24sYvwSUCT3f8Bx0f0JE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1027371376</pqid></control><display><type>article</type><title>Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma</title><source>Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list)</source><creator>Thoennissen, Nils H. ; Thoennissen, Gabriela B. ; Abbassi, Sam ; Nabavi-Nouis, Shayan ; Sauer, Tim ; Doan, Ngan B. ; Gery, Sigal ; Müller-Tidow, Carsten ; Said, Jonathan W. ; Koeffler, H. Phillip</creator><creatorcontrib>Thoennissen, Nils H. ; Thoennissen, Gabriela B. ; Abbassi, Sam ; Nabavi-Nouis, Shayan ; Sauer, Tim ; Doan, Ngan B. ; Gery, Sigal ; Müller-Tidow, Carsten ; Said, Jonathan W. ; Koeffler, H. Phillip</creatorcontrib><description>Abstract
Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathway in diffuse large B-cell lymphoma (DLBCL), one of the commonest types of mature B-cell lymphoma. Expression analysis of human B-cell lymphoma samples including DLBCL (n = 50), mantle cell (n = 21), follicular (n = 25) and Burkitt (n = 18) lymphoma revealed markedly down-regulated CEBPA and PER2 mRNA levels exclusively in DLBCL samples compared to control lymphatic tissue. We demonstrated direct regulation of the circadian core clock gene PER2 by C/EBPalpha in the pro-B cell line Ba/F3, and forced expression of PER2 resulted in decreased proliferation, G0/G1 cell cycle arrest and increased rates of apoptosis. Interestingly, treatment of human DLBCL cell lines with the histone deacetylase-inhibitor suberoylanilide hydroxamic acid (SAHA) significantly increased the expression of C/EBPalpha and Per2, accompanied by cell growth inhibition; in contrast, siRNA knockdown of CEBPA reduced the anti-proliferative effect of SAHA treatment. Our results show for the first time that C/EBPalpha with its associated direct core clock gene target, PER2, are highly deregulated in DLBCL, suggesting an important tumor suppressive pathway in the pathogenesis of this lymphoma entity.</description><identifier>ISSN: 1042-8194</identifier><identifier>EISSN: 1029-2403</identifier><identifier>DOI: 10.3109/10428194.2012.658792</identifier><identifier>PMID: 22260161</identifier><language>eng</language><publisher>United States: Informa Healthcare</publisher><subject>Apoptosis ; Biopsy ; CCAAT-Enhancer-Binding Protein-alpha - biosynthesis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Circadian Rhythm ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - metabolism ; mature B-cell lymphoma ; Models, Genetic ; Period Circadian Proteins - biosynthesis ; Transcription factor</subject><ispartof>Leukemia & lymphoma, 2012-08, Vol.53 (8), p.1577-1585</ispartof><rights>2012 Informa UK, Ltd. 2012</rights><rights>2012 lnforma UK, Ltd. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3</citedby><cites>FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22260161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thoennissen, Nils H.</creatorcontrib><creatorcontrib>Thoennissen, Gabriela B.</creatorcontrib><creatorcontrib>Abbassi, Sam</creatorcontrib><creatorcontrib>Nabavi-Nouis, Shayan</creatorcontrib><creatorcontrib>Sauer, Tim</creatorcontrib><creatorcontrib>Doan, Ngan B.</creatorcontrib><creatorcontrib>Gery, Sigal</creatorcontrib><creatorcontrib>Müller-Tidow, Carsten</creatorcontrib><creatorcontrib>Said, Jonathan W.</creatorcontrib><creatorcontrib>Koeffler, H. Phillip</creatorcontrib><title>Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma</title><title>Leukemia & lymphoma</title><addtitle>Leuk Lymphoma</addtitle><description>Abstract
Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathway in diffuse large B-cell lymphoma (DLBCL), one of the commonest types of mature B-cell lymphoma. Expression analysis of human B-cell lymphoma samples including DLBCL (n = 50), mantle cell (n = 21), follicular (n = 25) and Burkitt (n = 18) lymphoma revealed markedly down-regulated CEBPA and PER2 mRNA levels exclusively in DLBCL samples compared to control lymphatic tissue. We demonstrated direct regulation of the circadian core clock gene PER2 by C/EBPalpha in the pro-B cell line Ba/F3, and forced expression of PER2 resulted in decreased proliferation, G0/G1 cell cycle arrest and increased rates of apoptosis. Interestingly, treatment of human DLBCL cell lines with the histone deacetylase-inhibitor suberoylanilide hydroxamic acid (SAHA) significantly increased the expression of C/EBPalpha and Per2, accompanied by cell growth inhibition; in contrast, siRNA knockdown of CEBPA reduced the anti-proliferative effect of SAHA treatment. Our results show for the first time that C/EBPalpha with its associated direct core clock gene target, PER2, are highly deregulated in DLBCL, suggesting an important tumor suppressive pathway in the pathogenesis of this lymphoma entity.</description><subject>Apoptosis</subject><subject>Biopsy</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - biosynthesis</subject><subject>Cell Cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Circadian Rhythm</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - metabolism</subject><subject>mature B-cell lymphoma</subject><subject>Models, Genetic</subject><subject>Period Circadian Proteins - biosynthesis</subject><subject>Transcription factor</subject><issn>1042-8194</issn><issn>1029-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhSMEoqXwBgh5ySZTx_lzNkVlVH6kSiA0rK0b-zpxcezBcajmlXhKHE1b0U1XtuRzzj3XX5a9LeimLGh3XtCK8aKrNowWbNPUvO3Ys-y0oKzLWUXL5-u9YvmqOclezfMNpbTuGvYyO2GMNbRoitPs7y6Am2Uw-2i8Ixpk9IFst5eXu3N0IziJIe-NU8YNZB98ROMI2P0IBJwiyRiNBEukCRKUAUek9fIXUf7WzTEgTCRCGDCSAR2S71c_GIGAZDTDaA9EYcBhsRBRkRSsjNbLjMSuFvIxl2gtsYdpP_oJXmcvNNgZ39ydZ9nPT1e77Zf8-tvnr9vL61zWvI65lJ3uQCms2rLlPUesCs04bXrQvFdayVZK4NByzbCGWvFWIvK6rJSUquzLs-zimLtf-gmVRBcDWLEPZoJwEB6MePzizCgG_0eUvEn_zlPA-7uA4H8vOEcxmXldBRz6ZRYJUapWlG2TpNVRKoOf54D6YUxBxYpZ3GMWK2ZxxJxs7_6v-GC655oEH44C47QPE9z6YJWIcLA-6ERcmnmNf3LExaOEEcHGUSZ24sYvwSUCT3f8Bx0f0JE</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Thoennissen, Nils H.</creator><creator>Thoennissen, Gabriela B.</creator><creator>Abbassi, Sam</creator><creator>Nabavi-Nouis, Shayan</creator><creator>Sauer, Tim</creator><creator>Doan, Ngan B.</creator><creator>Gery, Sigal</creator><creator>Müller-Tidow, Carsten</creator><creator>Said, Jonathan W.</creator><creator>Koeffler, H. Phillip</creator><general>Informa Healthcare</general><general>Taylor & Francis</general><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><scope>5PM</scope></search><sort><creationdate>20120801</creationdate><title>Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma</title><author>Thoennissen, Nils H. ; Thoennissen, Gabriela B. ; Abbassi, Sam ; Nabavi-Nouis, Shayan ; Sauer, Tim ; Doan, Ngan B. ; Gery, Sigal ; Müller-Tidow, Carsten ; Said, Jonathan W. ; Koeffler, H. Phillip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Apoptosis</topic><topic>Biopsy</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - biosynthesis</topic><topic>Cell Cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Circadian Rhythm</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - metabolism</topic><topic>mature B-cell lymphoma</topic><topic>Models, Genetic</topic><topic>Period Circadian Proteins - biosynthesis</topic><topic>Transcription factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thoennissen, Nils H.</creatorcontrib><creatorcontrib>Thoennissen, Gabriela B.</creatorcontrib><creatorcontrib>Abbassi, Sam</creatorcontrib><creatorcontrib>Nabavi-Nouis, Shayan</creatorcontrib><creatorcontrib>Sauer, Tim</creatorcontrib><creatorcontrib>Doan, Ngan B.</creatorcontrib><creatorcontrib>Gery, Sigal</creatorcontrib><creatorcontrib>Müller-Tidow, Carsten</creatorcontrib><creatorcontrib>Said, Jonathan W.</creatorcontrib><creatorcontrib>Koeffler, H. Phillip</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia & lymphoma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thoennissen, Nils H.</au><au>Thoennissen, Gabriela B.</au><au>Abbassi, Sam</au><au>Nabavi-Nouis, Shayan</au><au>Sauer, Tim</au><au>Doan, Ngan B.</au><au>Gery, Sigal</au><au>Müller-Tidow, Carsten</au><au>Said, Jonathan W.</au><au>Koeffler, H. Phillip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma</atitle><jtitle>Leukemia & lymphoma</jtitle><addtitle>Leuk Lymphoma</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>53</volume><issue>8</issue><spage>1577</spage><epage>1585</epage><pages>1577-1585</pages><issn>1042-8194</issn><eissn>1029-2403</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>These authors contributed equally and should be considered first authors.</notes><abstract>Abstract
Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathway in diffuse large B-cell lymphoma (DLBCL), one of the commonest types of mature B-cell lymphoma. Expression analysis of human B-cell lymphoma samples including DLBCL (n = 50), mantle cell (n = 21), follicular (n = 25) and Burkitt (n = 18) lymphoma revealed markedly down-regulated CEBPA and PER2 mRNA levels exclusively in DLBCL samples compared to control lymphatic tissue. We demonstrated direct regulation of the circadian core clock gene PER2 by C/EBPalpha in the pro-B cell line Ba/F3, and forced expression of PER2 resulted in decreased proliferation, G0/G1 cell cycle arrest and increased rates of apoptosis. Interestingly, treatment of human DLBCL cell lines with the histone deacetylase-inhibitor suberoylanilide hydroxamic acid (SAHA) significantly increased the expression of C/EBPalpha and Per2, accompanied by cell growth inhibition; in contrast, siRNA knockdown of CEBPA reduced the anti-proliferative effect of SAHA treatment. Our results show for the first time that C/EBPalpha with its associated direct core clock gene target, PER2, are highly deregulated in DLBCL, suggesting an important tumor suppressive pathway in the pathogenesis of this lymphoma entity.</abstract><cop>United States</cop><pub>Informa Healthcare</pub><pmid>22260161</pmid><doi>10.3109/10428194.2012.658792</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1042-8194 |
| ispartof | Leukemia & lymphoma, 2012-08, Vol.53 (8), p.1577-1585 |
| issn | 1042-8194 1029-2403 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1027371376 |
| source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
| subjects | Apoptosis Biopsy CCAAT-Enhancer-Binding Protein-alpha - biosynthesis Cell Cycle Cell Line, Tumor Cell Proliferation Cell Survival Circadian Rhythm Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, Reporter Humans Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - metabolism mature B-cell lymphoma Models, Genetic Period Circadian Proteins - biosynthesis Transcription factor |
| title | Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T02%3A20%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_infor&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcription%20factor%20CCAAT/enhancer-binding%20protein%20alpha%20and%20critical%20circadian%20clock%20downstream%20target%20gene%20PER2%20are%20highly%20deregulated%20in%20diffuse%20large%20B-cell%20lymphoma&rft.jtitle=Leukemia%20&%20lymphoma&rft.au=Thoennissen,%20Nils%20H.&rft.date=2012-08-01&rft.volume=53&rft.issue=8&rft.spage=1577&rft.epage=1585&rft.pages=1577-1585&rft.issn=1042-8194&rft.eissn=1029-2403&rft_id=info:doi/10.3109/10428194.2012.658792&rft_dat=%3Cproquest_infor%3E1027371376%3C/proquest_infor%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c585t-cc9f9adde47378b8ee41f2806baf8bdfdc7cca8a78f2e5a5d87cee8534dccd3b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1027371376&rft_id=info:pmid/22260161&rfr_iscdi=true |