CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells
Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA...
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| Veröffentlicht in: | Journal of experimental & clinical cancer research 2014-11, Vol.33 |
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| creator | Zhang, Shulin Yang, Yi-Lin Wang, Yucheng You, Bin Dai, Yuyuan Chan, Geraldine Hsieh, David Kim, Il-Jin Fang, Li Tai Au, Alfred Stoppler, Hubert J Xu, Zhidong Jablons, David M You, Liang |
| description | Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA levels of CK2[alpha] and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay. Results In this study, we show that CK2[alpha] is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2[alpha] and Gli1 were broadly elevated and correlated (n=52, r=0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2[alpha] and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2[alpha] and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n=82, r=0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2[alpha] was silenced in two mesothelioma cell lines (H28 and H2052). CK2[alpha] siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2[alpha] inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2[alpha] resulted in an increase in Gli1 transcriptional activity in H28 cells. Conclusions Thus, we report for the first time that over-expressed CK2[alpha] positively regulate Hh/Gli1 signaling in human mesothelioma. Keywords: CK2[alpha], Hedgehog, Gli1, IHC, Mesothelioma |
| doi_str_mv | 10.1186/s13046-014-0093-6 |
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| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_1631623792</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A540660292</galeid><sourcerecordid>A540660292</sourcerecordid><originalsourceid>FETCH-LOGICAL-g952-577240dd0aa99bed38cac08695806aaa1377b6a335c43827b0cce2a1e449d61f3</originalsourceid><addsrcrecordid>eNptjktLw0AUhWehYK3-AHcDbps6j2SSWZaiVhTcdCcSbie3yZRJJmYSH1t_uakKdiF3ceDwfYdLyAVnc84zdRW4ZLGKGI8jxrSM1BGZMKlFpFmanZDTEHaMKa65npDP5b14AtdW8Dyj_hW7CN_bDkPAgtqGVkMNDa3B2bKBpqetw6EDR2sMvq_QWV_DjHZYDg56DHTs6AqLEitf0rCXnG1K2kJfvcHHfvHQpAadC2fkeAsu4PlvTsn65nq9XEUPj7d3y8VDVOpEREmaipgVBQPQeoOFzAwYlimdZEwBAJdpulEgZWJimYl0w4xBARzjWBeKb-WUXP7Mtp1_GTD0-c4P3fhgyLmSXAmZavFHleAwt83W9x2Y2gaTL5KYKcXENzX_hxqvwNoa3-DWjv2B8AWqtn1P</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1631623792</pqid></control><display><type>article</type><title>CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells</title><source>Springer Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>SpringerLink (Online service)</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><source>PubMed Central Open Access</source><creator>Zhang, Shulin ; Yang, Yi-Lin ; Wang, Yucheng ; You, Bin ; Dai, Yuyuan ; Chan, Geraldine ; Hsieh, David ; Kim, Il-Jin ; Fang, Li Tai ; Au, Alfred ; Stoppler, Hubert J ; Xu, Zhidong ; Jablons, David M ; You, Liang</creator><creatorcontrib>Zhang, Shulin ; Yang, Yi-Lin ; Wang, Yucheng ; You, Bin ; Dai, Yuyuan ; Chan, Geraldine ; Hsieh, David ; Kim, Il-Jin ; Fang, Li Tai ; Au, Alfred ; Stoppler, Hubert J ; Xu, Zhidong ; Jablons, David M ; You, Liang</creatorcontrib><description>Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA levels of CK2[alpha] and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay. Results In this study, we show that CK2[alpha] is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2[alpha] and Gli1 were broadly elevated and correlated (n=52, r=0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2[alpha] and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2[alpha] and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n=82, r=0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2[alpha] was silenced in two mesothelioma cell lines (H28 and H2052). CK2[alpha] siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2[alpha] inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2[alpha] resulted in an increase in Gli1 transcriptional activity in H28 cells. Conclusions Thus, we report for the first time that over-expressed CK2[alpha] positively regulate Hh/Gli1 signaling in human mesothelioma. Keywords: CK2[alpha], Hedgehog, Gli1, IHC, Mesothelioma</description><identifier>ISSN: 0392-9078</identifier><identifier>ISSN: 1756-9966</identifier><identifier>DOI: 10.1186/s13046-014-0093-6</identifier><language>eng</language><publisher>London: BioMed Central Ltd</publisher><subject>Analysis ; Cell growth ; Experiments ; Genes ; Health aspects ; Kinases ; Lung cancer ; Medical prognosis ; Physiological aspects ; Protein kinases ; Proteins ; Stem cells ; Studies ; Surgery ; Thoracic surgery ; Tumors</subject><ispartof>Journal of experimental & clinical cancer research, 2014-11, Vol.33</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Zhang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Zhang, Shulin</creatorcontrib><creatorcontrib>Yang, Yi-Lin</creatorcontrib><creatorcontrib>Wang, Yucheng</creatorcontrib><creatorcontrib>You, Bin</creatorcontrib><creatorcontrib>Dai, Yuyuan</creatorcontrib><creatorcontrib>Chan, Geraldine</creatorcontrib><creatorcontrib>Hsieh, David</creatorcontrib><creatorcontrib>Kim, Il-Jin</creatorcontrib><creatorcontrib>Fang, Li Tai</creatorcontrib><creatorcontrib>Au, Alfred</creatorcontrib><creatorcontrib>Stoppler, Hubert J</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Jablons, David M</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><title>CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells</title><title>Journal of experimental & clinical cancer research</title><description>Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA levels of CK2[alpha] and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay. Results In this study, we show that CK2[alpha] is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2[alpha] and Gli1 were broadly elevated and correlated (n=52, r=0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2[alpha] and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2[alpha] and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n=82, r=0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2[alpha] was silenced in two mesothelioma cell lines (H28 and H2052). CK2[alpha] siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2[alpha] inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2[alpha] resulted in an increase in Gli1 transcriptional activity in H28 cells. Conclusions Thus, we report for the first time that over-expressed CK2[alpha] positively regulate Hh/Gli1 signaling in human mesothelioma. Keywords: CK2[alpha], Hedgehog, Gli1, IHC, Mesothelioma</description><subject>Analysis</subject><subject>Cell growth</subject><subject>Experiments</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Medical prognosis</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Surgery</subject><subject>Thoracic surgery</subject><subject>Tumors</subject><issn>0392-9078</issn><issn>1756-9966</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNptjktLw0AUhWehYK3-AHcDbps6j2SSWZaiVhTcdCcSbie3yZRJJmYSH1t_uakKdiF3ceDwfYdLyAVnc84zdRW4ZLGKGI8jxrSM1BGZMKlFpFmanZDTEHaMKa65npDP5b14AtdW8Dyj_hW7CN_bDkPAgtqGVkMNDa3B2bKBpqetw6EDR2sMvq_QWV_DjHZYDg56DHTs6AqLEitf0rCXnG1K2kJfvcHHfvHQpAadC2fkeAsu4PlvTsn65nq9XEUPj7d3y8VDVOpEREmaipgVBQPQeoOFzAwYlimdZEwBAJdpulEgZWJimYl0w4xBARzjWBeKb-WUXP7Mtp1_GTD0-c4P3fhgyLmSXAmZavFHleAwt83W9x2Y2gaTL5KYKcXENzX_hxqvwNoa3-DWjv2B8AWqtn1P</recordid><startdate>20141125</startdate><enddate>20141125</enddate><creator>Zhang, Shulin</creator><creator>Yang, Yi-Lin</creator><creator>Wang, Yucheng</creator><creator>You, Bin</creator><creator>Dai, Yuyuan</creator><creator>Chan, Geraldine</creator><creator>Hsieh, David</creator><creator>Kim, Il-Jin</creator><creator>Fang, Li Tai</creator><creator>Au, Alfred</creator><creator>Stoppler, Hubert J</creator><creator>Xu, Zhidong</creator><creator>Jablons, David M</creator><creator>You, Liang</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20141125</creationdate><title>CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells</title><author>Zhang, Shulin ; Yang, Yi-Lin ; Wang, Yucheng ; You, Bin ; Dai, Yuyuan ; Chan, Geraldine ; Hsieh, David ; Kim, Il-Jin ; Fang, Li Tai ; Au, Alfred ; Stoppler, Hubert J ; Xu, Zhidong ; Jablons, David M ; You, Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g952-577240dd0aa99bed38cac08695806aaa1377b6a335c43827b0cce2a1e449d61f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Cell growth</topic><topic>Experiments</topic><topic>Genes</topic><topic>Health aspects</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Medical prognosis</topic><topic>Physiological aspects</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Surgery</topic><topic>Thoracic surgery</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Shulin</creatorcontrib><creatorcontrib>Yang, Yi-Lin</creatorcontrib><creatorcontrib>Wang, Yucheng</creatorcontrib><creatorcontrib>You, Bin</creatorcontrib><creatorcontrib>Dai, Yuyuan</creatorcontrib><creatorcontrib>Chan, Geraldine</creatorcontrib><creatorcontrib>Hsieh, David</creatorcontrib><creatorcontrib>Kim, Il-Jin</creatorcontrib><creatorcontrib>Fang, Li Tai</creatorcontrib><creatorcontrib>Au, Alfred</creatorcontrib><creatorcontrib>Stoppler, Hubert J</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Jablons, David M</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of experimental & clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Shulin</au><au>Yang, Yi-Lin</au><au>Wang, Yucheng</au><au>You, Bin</au><au>Dai, Yuyuan</au><au>Chan, Geraldine</au><au>Hsieh, David</au><au>Kim, Il-Jin</au><au>Fang, Li Tai</au><au>Au, Alfred</au><au>Stoppler, Hubert J</au><au>Xu, Zhidong</au><au>Jablons, David M</au><au>You, Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells</atitle><jtitle>Journal of experimental & clinical cancer research</jtitle><date>2014-11-25</date><risdate>2014</risdate><volume>33</volume><issn>0392-9078</issn><issn>1756-9966</issn><abstract>Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA levels of CK2[alpha] and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay. Results In this study, we show that CK2[alpha] is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2[alpha] and Gli1 were broadly elevated and correlated (n=52, r=0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2[alpha] and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2[alpha] and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n=82, r=0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2[alpha] was silenced in two mesothelioma cell lines (H28 and H2052). CK2[alpha] siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2[alpha] inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2[alpha] resulted in an increase in Gli1 transcriptional activity in H28 cells. Conclusions Thus, we report for the first time that over-expressed CK2[alpha] positively regulate Hh/Gli1 signaling in human mesothelioma. Keywords: CK2[alpha], Hedgehog, Gli1, IHC, Mesothelioma</abstract><cop>London</cop><pub>BioMed Central Ltd</pub><doi>10.1186/s13046-014-0093-6</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Cell growth Experiments Genes Health aspects Kinases Lung cancer Medical prognosis Physiological aspects Protein kinases Proteins Stem cells Studies Surgery Thoracic surgery Tumors |
| title | CK2[alpha], over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells |
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