Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity
SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell g...
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| Veröffentlicht in: | Clinical cancer research 2010-09, Vol.16 (17), p.4363-4373 |
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| creator | SHIH SHENG JIANG FANG, Wen-Tsen LI, Yu-Wei JANG, Te-Hsuan CHAN, Shih-Hsuan SU JING YANG HSIUNG, Chao A WU, Cheng-Wen WANG, Lu-Hai CHANG, I-Shou HOU, Ya-Hsiue HUANG, Shiu-Feng LINJU YEN, B CHANG, Junn-Liang LI, Shih-Miao LIU, Hui-Ping LIU, Ying-Lan HUANG, Chih-Ting |
| description | SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.
Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4. |
| doi_str_mv | 10.1158/1078-0432.ccr-10-0138 |
| format | Article |
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Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.ccr-10-0138</identifier><identifier>PMID: 20651055</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase 4 - genetics ; Cyclin-Dependent Kinase 4 - metabolism ; Cyclin-Dependent Kinase Inhibitor p21 - genetics ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Down-Regulation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Liver Neoplasms, Experimental - genetics ; Liver Neoplasms, Experimental - metabolism ; Liver Neoplasms, Experimental - pathology ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Medical sciences ; Mice ; Mice, SCID ; Oligonucleotide Array Sequence Analysis ; Pharmacology. Drug treatments ; Pneumology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Transplantation, Heterologous ; Tumor Burden ; Tumors of the respiratory system and mediastinum ; Up-Regulation</subject><ispartof>Clinical cancer research, 2010-09, Vol.16 (17), p.4363-4373</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-a30dc78c4a3780dddef782b140d6125df9aeb60afb9faae477716cf60064111d3</citedby><cites>FETCH-LOGICAL-c451t-a30dc78c4a3780dddef782b140d6125df9aeb60afb9faae477716cf60064111d3</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=23187039$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20651055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SHIH SHENG JIANG</creatorcontrib><creatorcontrib>FANG, Wen-Tsen</creatorcontrib><creatorcontrib>LI, Yu-Wei</creatorcontrib><creatorcontrib>JANG, Te-Hsuan</creatorcontrib><creatorcontrib>CHAN, Shih-Hsuan</creatorcontrib><creatorcontrib>SU JING YANG</creatorcontrib><creatorcontrib>HSIUNG, Chao A</creatorcontrib><creatorcontrib>WU, Cheng-Wen</creatorcontrib><creatorcontrib>WANG, Lu-Hai</creatorcontrib><creatorcontrib>CHANG, I-Shou</creatorcontrib><creatorcontrib>HOU, Ya-Hsiue</creatorcontrib><creatorcontrib>HUANG, Shiu-Feng</creatorcontrib><creatorcontrib>LINJU YEN, B</creatorcontrib><creatorcontrib>CHANG, Junn-Liang</creatorcontrib><creatorcontrib>LI, Shih-Miao</creatorcontrib><creatorcontrib>LIU, Hui-Ping</creatorcontrib><creatorcontrib>LIU, Ying-Lan</creatorcontrib><creatorcontrib>HUANG, Chih-Ting</creatorcontrib><title>Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.
Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cyclin-Dependent Kinase 4 - genetics</subject><subject>Cyclin-Dependent Kinase 4 - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Down-Regulation</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Liver Neoplasms, Experimental - genetics</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Liver Neoplasms, Experimental - pathology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - metabolism</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Burden</subject><subject>Tumors of the respiratory system and mediastinum</subject><subject>Up-Regulation</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1P3DAQhq2qVaHATwD5UvUUOhPbcXJEEdCVVkKiIPUWef2xGCX2Yicg_n2TsrTqaUaj550ZPYScIpwjivo7gqwL4Kw81zoVCAUgqz-QQxRCFqysxMe5f2cOyJecHwGQI_DP5KCESiAIcUjy_S7Z7dSr0cdAo6M_b3411Ae6nsKWXhgbolZJ-xAHRVUwdDVmugrPsX-2gw3jgo4Plt7-t6S1fU-vU3wZH_6E7qYhJr-1wWs_vh6TT0712Z7s6xG5v7q8a38U65vrVXuxLjQXOBaKgdGy1lwxWYMxxjpZlxvkYCoshXGNspsKlNs0TinLpZRYaVcBVBwRDTsi39727lJ8mmweu8FnPb-mgo1T7qTgUJYNNDMp3kidYs7Jum6X_KDSa4fQLbq7RWW3qOza9naZLrrn3Nn-wrQZrPmbevc7A1_3gMpa9S6poH3-xzGsJbCG_Qb6tolu</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>SHIH SHENG JIANG</creator><creator>FANG, Wen-Tsen</creator><creator>LI, Yu-Wei</creator><creator>JANG, Te-Hsuan</creator><creator>CHAN, Shih-Hsuan</creator><creator>SU JING YANG</creator><creator>HSIUNG, Chao A</creator><creator>WU, Cheng-Wen</creator><creator>WANG, Lu-Hai</creator><creator>CHANG, I-Shou</creator><creator>HOU, Ya-Hsiue</creator><creator>HUANG, Shiu-Feng</creator><creator>LINJU YEN, B</creator><creator>CHANG, Junn-Liang</creator><creator>LI, Shih-Miao</creator><creator>LIU, Hui-Ping</creator><creator>LIU, Ying-Lan</creator><creator>HUANG, Chih-Ting</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>20100901</creationdate><title>Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity</title><author>SHIH SHENG JIANG ; FANG, Wen-Tsen ; LI, Yu-Wei ; JANG, Te-Hsuan ; CHAN, Shih-Hsuan ; SU JING YANG ; HSIUNG, Chao A ; WU, Cheng-Wen ; WANG, Lu-Hai ; CHANG, I-Shou ; HOU, Ya-Hsiue ; HUANG, Shiu-Feng ; LINJU YEN, B ; CHANG, Junn-Liang ; LI, Shih-Miao ; LIU, Hui-Ping ; LIU, Ying-Lan ; HUANG, Chih-Ting</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-a30dc78c4a3780dddef782b140d6125df9aeb60afb9faae477716cf60064111d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cyclin-Dependent Kinase 4 - genetics</topic><topic>Cyclin-Dependent Kinase 4 - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Down-Regulation</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Liver Neoplasms, Experimental - genetics</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Liver Neoplasms, Experimental - pathology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>SOX9 Transcription Factor - metabolism</topic><topic>Transplantation, Heterologous</topic><topic>Tumor Burden</topic><topic>Tumors of the respiratory system and mediastinum</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHIH SHENG JIANG</creatorcontrib><creatorcontrib>FANG, Wen-Tsen</creatorcontrib><creatorcontrib>LI, Yu-Wei</creatorcontrib><creatorcontrib>JANG, Te-Hsuan</creatorcontrib><creatorcontrib>CHAN, Shih-Hsuan</creatorcontrib><creatorcontrib>SU JING YANG</creatorcontrib><creatorcontrib>HSIUNG, Chao A</creatorcontrib><creatorcontrib>WU, Cheng-Wen</creatorcontrib><creatorcontrib>WANG, Lu-Hai</creatorcontrib><creatorcontrib>CHANG, I-Shou</creatorcontrib><creatorcontrib>HOU, Ya-Hsiue</creatorcontrib><creatorcontrib>HUANG, Shiu-Feng</creatorcontrib><creatorcontrib>LINJU YEN, B</creatorcontrib><creatorcontrib>CHANG, Junn-Liang</creatorcontrib><creatorcontrib>LI, Shih-Miao</creatorcontrib><creatorcontrib>LIU, Hui-Ping</creatorcontrib><creatorcontrib>LIU, Ying-Lan</creatorcontrib><creatorcontrib>HUANG, Chih-Ting</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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SHIH SHENG JIANG</au><au>FANG, Wen-Tsen</au><au>LI, Yu-Wei</au><au>JANG, Te-Hsuan</au><au>CHAN, Shih-Hsuan</au><au>SU JING YANG</au><au>HSIUNG, Chao A</au><au>WU, Cheng-Wen</au><au>WANG, Lu-Hai</au><au>CHANG, I-Shou</au><au>HOU, Ya-Hsiue</au><au>HUANG, Shiu-Feng</au><au>LINJU YEN, B</au><au>CHANG, Junn-Liang</au><au>LI, Shih-Miao</au><au>LIU, Hui-Ping</au><au>LIU, Ying-Lan</au><au>HUANG, Chih-Ting</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>16</volume><issue>17</issue><spage>4363</spage><epage>4373</epage><pages>4363-4373</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.
Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>20651055</pmid><doi>10.1158/1078-0432.ccr-10-0138</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - pathology Animals Antineoplastic agents Biological and medical sciences Blotting, Western Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase 4 - genetics Cyclin-Dependent Kinase 4 - metabolism Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Down-Regulation Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Liver Neoplasms, Experimental - genetics Liver Neoplasms, Experimental - metabolism Liver Neoplasms, Experimental - pathology Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Medical sciences Mice Mice, SCID Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Pneumology Reverse Transcriptase Polymerase Chain Reaction RNA Interference SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism Transplantation, Heterologous Tumor Burden Tumors of the respiratory system and mediastinum Up-Regulation |
| title | Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity |
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