Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma
Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in ...
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Veröffentlicht in: | Journal of cellular and molecular medicine 2015-10, Vol.19 (10), p.2385-2396 |
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description | Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P |
doi_str_mv | 10.1111/jcmm.12620 |
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Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.12620</identifier><identifier>PMID: 26218750</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Artificial chromosomes ; BASIC BIOLOGICAL SCIENCES ; Case-Control Studies ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Chi-Square Distribution ; Copy number ; Cul4A ; Cullin Proteins - genetics ; Cullin Proteins - metabolism ; Fluorescence ; Fluorescence in situ hybridization ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Gli1 ; hedgehog signalling ; Humans ; Hybridization ; Hybridization analysis ; Immunohistochemistry ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; malignant pleural mesothelioma ; Medical prognosis ; Medical research ; Mesothelioma ; Mesothelioma - genetics ; Mesothelioma - metabolism ; Mesothelioma - pathology ; Mesothelioma, Malignant ; mTOR ; Original ; Pleural Neoplasms - metabolism ; Pleural Neoplasms - pathology ; Protein expression ; Proteins ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; siRNA ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumors ; Zinc Finger Protein GLI1</subject><ispartof>Journal of cellular and molecular medicine, 2015-10, Vol.19 (10), p.2385-2396</ispartof><rights>2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4750-d489bcdaa77a85e4bb54c014dc32cbd9025308b6113e72ae7231ec081c0e669f3</citedby><cites>FETCH-LOGICAL-c4750-d489bcdaa77a85e4bb54c014dc32cbd9025308b6113e72ae7231ec081c0e669f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594680/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594680/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26218750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/servlets/purl/1213428$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Yi‐Lin</creatorcontrib><creatorcontrib>Ni, Jian</creatorcontrib><creatorcontrib>Hsu, Ping‐Chih</creatorcontrib><creatorcontrib>Mao, Jian‐Hua</creatorcontrib><creatorcontrib>Hsieh, David</creatorcontrib><creatorcontrib>Xu, Angela</creatorcontrib><creatorcontrib>Chan, Geraldine</creatorcontrib><creatorcontrib>Au, Alfred</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Jablons, David M.</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><creatorcontrib>Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)</creatorcontrib><title>Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.</description><subject>Artificial chromosomes</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Case-Control Studies</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Chi-Square Distribution</subject><subject>Copy number</subject><subject>Cul4A</subject><subject>Cullin Proteins - genetics</subject><subject>Cullin Proteins - metabolism</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Gene Dosage</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gli1</subject><subject>hedgehog signalling</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Hybridization analysis</subject><subject>Immunohistochemistry</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>malignant pleural mesothelioma</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Mesothelioma</subject><subject>Mesothelioma - genetics</subject><subject>Mesothelioma - metabolism</subject><subject>Mesothelioma - pathology</subject><subject>Mesothelioma, Malignant</subject><subject>mTOR</subject><subject>Original</subject><subject>Pleural Neoplasms - metabolism</subject><subject>Pleural Neoplasms - pathology</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>siRNA</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumors</subject><subject>Zinc Finger Protein GLI1</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUFrFDEUx4MotlYvfgAZ9CLC1rwkM5O5CGXR1tLiRb2GTOZtN0smWZNMa7-9WWdbag8GQgLvx--95E_Ia6DHUNbHjRnHY2ANo0_IIdSSLUTHxdP9HSSXB-RFShtKeQO8e04OCguyrekh-bmcnDipwjVG_L2NmJINvtIpBWN1xqG6sXldnToL1YO69dWonb3y2udq63CK2lUjppDX6GwY9UvybKVdwlf784j8-PL5-_JscfHt9Ovy5GJhRGm_GITsejNo3bZa1ij6vhaGghgMZ6YfOspqTmXfAHBsmS6bAxoqwVBsmm7Fj8in2bud-hEHgz6XUdQ22lHHWxW0Vf9WvF2rq3CtRN2JRtIieDsLQspWJWMzmrUJ3qPJChhwwWSB3u-7xPBrwpTVaJNB57THMCUFLbRC8pbtfO8eoZswRV_-QDHWUVG3rGOF-jBTJoaUIq7uJwaqdpmqXabqb6YFfvPwjffoXYgFgBm4sQ5v_6NS58vLy1n6B9gYrOU</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Yang, Yi‐Lin</creator><creator>Ni, Jian</creator><creator>Hsu, Ping‐Chih</creator><creator>Mao, Jian‐Hua</creator><creator>Hsieh, David</creator><creator>Xu, Angela</creator><creator>Chan, Geraldine</creator><creator>Au, Alfred</creator><creator>Xu, Zhidong</creator><creator>Jablons, David M.</creator><creator>You, Liang</creator><general>John Wiley & Sons, Inc</general><general>John Wiley & Sons, Ltd</general><scope>24P</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>201510</creationdate><title>Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma</title><author>Yang, Yi‐Lin ; Ni, Jian ; Hsu, Ping‐Chih ; Mao, Jian‐Hua ; Hsieh, David ; Xu, Angela ; Chan, Geraldine ; Au, Alfred ; Xu, Zhidong ; Jablons, David M. ; You, Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4750-d489bcdaa77a85e4bb54c014dc32cbd9025308b6113e72ae7231ec081c0e669f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Artificial chromosomes</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Case-Control Studies</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Chi-Square Distribution</topic><topic>Copy number</topic><topic>Cul4A</topic><topic>Cullin Proteins - genetics</topic><topic>Cullin Proteins - metabolism</topic><topic>Fluorescence</topic><topic>Fluorescence in situ hybridization</topic><topic>Gene Dosage</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gli1</topic><topic>hedgehog signalling</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Hybridization analysis</topic><topic>Immunohistochemistry</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>malignant pleural mesothelioma</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Mesothelioma</topic><topic>Mesothelioma - genetics</topic><topic>Mesothelioma - metabolism</topic><topic>Mesothelioma - pathology</topic><topic>Mesothelioma, Malignant</topic><topic>mTOR</topic><topic>Original</topic><topic>Pleural Neoplasms - metabolism</topic><topic>Pleural Neoplasms - pathology</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>siRNA</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tumors</topic><topic>Zinc Finger Protein GLI1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yi‐Lin</creatorcontrib><creatorcontrib>Ni, Jian</creatorcontrib><creatorcontrib>Hsu, Ping‐Chih</creatorcontrib><creatorcontrib>Mao, Jian‐Hua</creatorcontrib><creatorcontrib>Hsieh, David</creatorcontrib><creatorcontrib>Xu, Angela</creatorcontrib><creatorcontrib>Chan, Geraldine</creatorcontrib><creatorcontrib>Au, Alfred</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Jablons, David M.</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><creatorcontrib>Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV - Hybrid</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Yi‐Lin</au><au>Ni, Jian</au><au>Hsu, Ping‐Chih</au><au>Mao, Jian‐Hua</au><au>Hsieh, David</au><au>Xu, Angela</au><au>Chan, Geraldine</au><au>Au, Alfred</au><au>Xu, Zhidong</au><au>Jablons, David M.</au><au>You, Liang</au><aucorp>Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2015-10</date><risdate>2015</risdate><volume>19</volume><issue>10</issue><spage>2385</spage><epage>2396</epage><pages>2385-2396</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>26218750</pmid><doi>10.1111/jcmm.12620</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Artificial chromosomes BASIC BIOLOGICAL SCIENCES Case-Control Studies Cell cycle Cell growth Cell Line, Tumor Chi-Square Distribution Copy number Cul4A Cullin Proteins - genetics Cullin Proteins - metabolism Fluorescence Fluorescence in situ hybridization Gene Dosage Gene Expression Regulation, Neoplastic Gli1 hedgehog signalling Humans Hybridization Hybridization analysis Immunohistochemistry Lung cancer Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology malignant pleural mesothelioma Medical prognosis Medical research Mesothelioma Mesothelioma - genetics Mesothelioma - metabolism Mesothelioma - pathology Mesothelioma, Malignant mTOR Original Pleural Neoplasms - metabolism Pleural Neoplasms - pathology Protein expression Proteins Real-Time Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism siRNA Transcription Factors - genetics Transcription Factors - metabolism Tumors Zinc Finger Protein GLI1 |
title | Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma |
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