Inhibitory role of peroxisome proliferator‐activated receptor gamma in hepatocarcinogenesis in mice and in vitro
Although peroxisome proliferator‐activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ‐deficient (PPARγ+/−) and wi...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2010-06, Vol.51 (6), p.2008-2019 |
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| creator | Yu, Jun Shen, Bo Chu, Eagle S. H. Teoh, Narci Cheung, Kin‐Fai Wu, Chung‐Wah Wang, Shiyan Lam, Cleo N. Y. Feng, Hai Zhao, Junhong Cheng, Alfred S. L. To, Ka‐Fai Chan, Henry L. Y. Sung, Joseph J. Y. |
| description | Although peroxisome proliferator‐activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ‐deficient (PPARγ+/−) and wild‐type (PPARγ+/+) littermates were used in a diethylnitrosamine (DEN)‐induced HCC model and treated with PPARγ agonist (rosiglitazone) or the vehicle alone for 8 months. The effects of PPARγ on HCC cell growth and apoptosis were examined using PPARγ‐expressing adenovirus (Ad‐PPARγ). PPARγ+/− mice were more susceptible to DEN‐induced HCC than PPARγ+/+ mice (94% versus 62%, P < 0.05), and rosiglitazone significantly reduced the incidence of HCC in PPARγ+/+ mice (vehicle 62% versus treatment 24%, P < 0.01), but not in PPARγ+/− mice, indicating that PPARγ suppresses hepatocellular carcinogenesis. A pronounced expression of PPARγ was observed in a HCC cell line (Hep3B) infected with Ad‐PPARγ. Such induction markedly suppressed HCC cell viability (P < 0.01). Further, Hep3B infection with Ad‐PPARγ revealed a decreased proportion of cells in S‐phase (12.92% versus 11.58%, P < 0.05), with arrest at G2/M phase (38.2% versus 55.68%, P < 0.001), and there was concomitant phosphorylation of the key G2/M phase inhibitors cdc25C and cdc2. PPARγ overexpression increased cell apoptosis (21.47% versus 35.02%, P < 0.01), mediated by both extrinsic (Fas and tumor necrosis factor‐α) and intrinsic (caspase‐9, caspase‐3, caspase‐7, and poly[ADP‐ribose] polymerase) pathways. Moreover, PPARγ directly induced a putative tumor suppressor gene, growth differentiation factor‐15. Conclusion: Loss of one PPARγ allele is sufficient to enhance susceptibility to HCC. PPARγ suppresses tumor cell growth through reducing cell proliferation and inducing G2/M phase arrest, apoptosis, and up‐regulating growth differentiation factor‐15. Thus, PPARγ acts as a tumor‐suppressor gene in the liver. HEPATOLOGY 2010 |
| doi_str_mv | 10.1002/hep.23550 |
| format | Article |
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H. ; Teoh, Narci ; Cheung, Kin‐Fai ; Wu, Chung‐Wah ; Wang, Shiyan ; Lam, Cleo N. Y. ; Feng, Hai ; Zhao, Junhong ; Cheng, Alfred S. L. ; To, Ka‐Fai ; Chan, Henry L. Y. ; Sung, Joseph J. Y.</creator><creatorcontrib>Yu, Jun ; Shen, Bo ; Chu, Eagle S. H. ; Teoh, Narci ; Cheung, Kin‐Fai ; Wu, Chung‐Wah ; Wang, Shiyan ; Lam, Cleo N. Y. ; Feng, Hai ; Zhao, Junhong ; Cheng, Alfred S. L. ; To, Ka‐Fai ; Chan, Henry L. Y. ; Sung, Joseph J. Y.</creatorcontrib><description><![CDATA[Although peroxisome proliferator‐activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ‐deficient (PPARγ+/−) and wild‐type (PPARγ+/+) littermates were used in a diethylnitrosamine (DEN)‐induced HCC model and treated with PPARγ agonist (rosiglitazone) or the vehicle alone for 8 months. The effects of PPARγ on HCC cell growth and apoptosis were examined using PPARγ‐expressing adenovirus (Ad‐PPARγ). PPARγ+/− mice were more susceptible to DEN‐induced HCC than PPARγ+/+ mice (94% versus 62%, P < 0.05), and rosiglitazone significantly reduced the incidence of HCC in PPARγ+/+ mice (vehicle 62% versus treatment 24%, P < 0.01), but not in PPARγ+/− mice, indicating that PPARγ suppresses hepatocellular carcinogenesis. A pronounced expression of PPARγ was observed in a HCC cell line (Hep3B) infected with Ad‐PPARγ. Such induction markedly suppressed HCC cell viability (P < 0.01). Further, Hep3B infection with Ad‐PPARγ revealed a decreased proportion of cells in S‐phase (12.92% versus 11.58%, P < 0.05), with arrest at G2/M phase (38.2% versus 55.68%, P < 0.001), and there was concomitant phosphorylation of the key G2/M phase inhibitors cdc25C and cdc2. PPARγ overexpression increased cell apoptosis (21.47% versus 35.02%, P < 0.01), mediated by both extrinsic (Fas and tumor necrosis factor‐α) and intrinsic (caspase‐9, caspase‐3, caspase‐7, and poly[ADP‐ribose] polymerase) pathways. Moreover, PPARγ directly induced a putative tumor suppressor gene, growth differentiation factor‐15. Conclusion: Loss of one PPARγ allele is sufficient to enhance susceptibility to HCC. PPARγ suppresses tumor cell growth through reducing cell proliferation and inducing G2/M phase arrest, apoptosis, and up‐regulating growth differentiation factor‐15. Thus, PPARγ acts as a tumor‐suppressor gene in the liver. HEPATOLOGY 2010]]></description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.23550</identifier><identifier>PMID: 20512989</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenoviridae ; Adenovirus ; Alkylating Agents ; Animals ; Apoptosis ; Biological and medical sciences ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - prevention & control ; Cell Cycle ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Diethylnitrosamine ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Profiling ; Genes ; Growth Differentiation Factor 15 - metabolism ; Hepatology ; Humans ; Hypoglycemic Agents - therapeutic use ; Liver Neoplasms, Experimental - genetics ; Liver Neoplasms, Experimental - metabolism ; Liver Neoplasms, Experimental - prevention & control ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; PPAR gamma - agonists ; PPAR gamma - genetics ; PPAR gamma - metabolism ; Thiazolidinediones - therapeutic use ; Tumors ; Up-Regulation</subject><ispartof>Hepatology (Baltimore, Md.), 2010-06, Vol.51 (6), p.2008-2019</ispartof><rights>Copyright © 2010 American Association for the Study of Liver Diseases</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5160-fb46964caabe81d38a2590622babaf159e9d8bacb0a54f773337d563ea788b613</citedby><cites>FETCH-LOGICAL-c5160-fb46964caabe81d38a2590622babaf159e9d8bacb0a54f773337d563ea788b613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.23550$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.23550$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22901375$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20512989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Shen, Bo</creatorcontrib><creatorcontrib>Chu, Eagle S. H.</creatorcontrib><creatorcontrib>Teoh, Narci</creatorcontrib><creatorcontrib>Cheung, Kin‐Fai</creatorcontrib><creatorcontrib>Wu, Chung‐Wah</creatorcontrib><creatorcontrib>Wang, Shiyan</creatorcontrib><creatorcontrib>Lam, Cleo N. Y.</creatorcontrib><creatorcontrib>Feng, Hai</creatorcontrib><creatorcontrib>Zhao, Junhong</creatorcontrib><creatorcontrib>Cheng, Alfred S. L.</creatorcontrib><creatorcontrib>To, Ka‐Fai</creatorcontrib><creatorcontrib>Chan, Henry L. Y.</creatorcontrib><creatorcontrib>Sung, Joseph J. Y.</creatorcontrib><title>Inhibitory role of peroxisome proliferator‐activated receptor gamma in hepatocarcinogenesis in mice and in vitro</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description><![CDATA[Although peroxisome proliferator‐activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ‐deficient (PPARγ+/−) and wild‐type (PPARγ+/+) littermates were used in a diethylnitrosamine (DEN)‐induced HCC model and treated with PPARγ agonist (rosiglitazone) or the vehicle alone for 8 months. The effects of PPARγ on HCC cell growth and apoptosis were examined using PPARγ‐expressing adenovirus (Ad‐PPARγ). PPARγ+/− mice were more susceptible to DEN‐induced HCC than PPARγ+/+ mice (94% versus 62%, P < 0.05), and rosiglitazone significantly reduced the incidence of HCC in PPARγ+/+ mice (vehicle 62% versus treatment 24%, P < 0.01), but not in PPARγ+/− mice, indicating that PPARγ suppresses hepatocellular carcinogenesis. A pronounced expression of PPARγ was observed in a HCC cell line (Hep3B) infected with Ad‐PPARγ. Such induction markedly suppressed HCC cell viability (P < 0.01). Further, Hep3B infection with Ad‐PPARγ revealed a decreased proportion of cells in S‐phase (12.92% versus 11.58%, P < 0.05), with arrest at G2/M phase (38.2% versus 55.68%, P < 0.001), and there was concomitant phosphorylation of the key G2/M phase inhibitors cdc25C and cdc2. PPARγ overexpression increased cell apoptosis (21.47% versus 35.02%, P < 0.01), mediated by both extrinsic (Fas and tumor necrosis factor‐α) and intrinsic (caspase‐9, caspase‐3, caspase‐7, and poly[ADP‐ribose] polymerase) pathways. Moreover, PPARγ directly induced a putative tumor suppressor gene, growth differentiation factor‐15. Conclusion: Loss of one PPARγ allele is sufficient to enhance susceptibility to HCC. PPARγ suppresses tumor cell growth through reducing cell proliferation and inducing G2/M phase arrest, apoptosis, and up‐regulating growth differentiation factor‐15. Thus, PPARγ acts as a tumor‐suppressor gene in the liver. HEPATOLOGY 2010]]></description><subject>Adenoviridae</subject><subject>Adenovirus</subject><subject>Alkylating Agents</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - prevention & control</subject><subject>Cell Cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Diethylnitrosamine</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Growth Differentiation Factor 15 - metabolism</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Liver Neoplasms, Experimental - genetics</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Liver Neoplasms, Experimental - prevention & control</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>PPAR gamma - agonists</subject><subject>PPAR gamma - genetics</subject><subject>PPAR gamma - metabolism</subject><subject>Thiazolidinediones - therapeutic use</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10c1qFTEUAOAgFnutLnwBCYigi2nzM0kmy1KqLRTqQtfDSeZMmzIzGZO51bvzEXxGn8Rc77WC0FXC4eP8EvKKs2POmDi5xflYSKXYE7LiSphKSsWekhUThlWWS3tInud8xxiztWiekUPBFBe2sSuSLqfb4MIS04amOCCNPZ0xxe8hxxHpXGKhxwQF_PrxE_wS7mHBjib0OJcgvYFxBBomWpooykPyYYo3OGEOeRsfg0cKU7f934clxRfkoIch48v9e0S-fDj_fHZRXV1_vDw7vaq84ppVvau11bUHcNjwTjYglGVaCAcOeq4s2q5x4B0DVffGSClNp7REME3jNJdH5N0ubxni6xrz0o4hexwGmDCuc8uN0Vo3SshC3_xH7-I6TaW7oooRQtXbhO93yqeYc8K-nVMYIW1aztrtIdqyg_bPIYp9vc-4diN2D_Lv5gt4uweQPQx9gsmH_M8Jy7g0qriTnfsWBtw8XrG9OP-0K_0bXWGhSg</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Yu, Jun</creator><creator>Shen, Bo</creator><creator>Chu, Eagle S. H.</creator><creator>Teoh, Narci</creator><creator>Cheung, Kin‐Fai</creator><creator>Wu, Chung‐Wah</creator><creator>Wang, Shiyan</creator><creator>Lam, Cleo N. Y.</creator><creator>Feng, Hai</creator><creator>Zhao, Junhong</creator><creator>Cheng, Alfred S. L.</creator><creator>To, Ka‐Fai</creator><creator>Chan, Henry L. Y.</creator><creator>Sung, Joseph J. Y.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201006</creationdate><title>Inhibitory role of peroxisome proliferator‐activated receptor gamma in hepatocarcinogenesis in mice and in vitro</title><author>Yu, Jun ; Shen, Bo ; Chu, Eagle S. H. ; Teoh, Narci ; Cheung, Kin‐Fai ; Wu, Chung‐Wah ; Wang, Shiyan ; Lam, Cleo N. Y. ; Feng, Hai ; Zhao, Junhong ; Cheng, Alfred S. L. ; To, Ka‐Fai ; Chan, Henry L. Y. ; Sung, Joseph J. Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5160-fb46964caabe81d38a2590622babaf159e9d8bacb0a54f773337d563ea788b613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenoviridae</topic><topic>Adenovirus</topic><topic>Alkylating Agents</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - prevention & control</topic><topic>Cell Cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Diethylnitrosamine</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Growth Differentiation Factor 15 - metabolism</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Liver Neoplasms, Experimental - genetics</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Liver Neoplasms, Experimental - prevention & control</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>PPAR gamma - agonists</topic><topic>PPAR gamma - genetics</topic><topic>PPAR gamma - metabolism</topic><topic>Thiazolidinediones - therapeutic use</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Shen, Bo</creatorcontrib><creatorcontrib>Chu, Eagle S. H.</creatorcontrib><creatorcontrib>Teoh, Narci</creatorcontrib><creatorcontrib>Cheung, Kin‐Fai</creatorcontrib><creatorcontrib>Wu, Chung‐Wah</creatorcontrib><creatorcontrib>Wang, Shiyan</creatorcontrib><creatorcontrib>Lam, Cleo N. Y.</creatorcontrib><creatorcontrib>Feng, Hai</creatorcontrib><creatorcontrib>Zhao, Junhong</creatorcontrib><creatorcontrib>Cheng, Alfred S. L.</creatorcontrib><creatorcontrib>To, Ka‐Fai</creatorcontrib><creatorcontrib>Chan, Henry L. Y.</creatorcontrib><creatorcontrib>Sung, Joseph J. Y.</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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Jun</au><au>Shen, Bo</au><au>Chu, Eagle S. H.</au><au>Teoh, Narci</au><au>Cheung, Kin‐Fai</au><au>Wu, Chung‐Wah</au><au>Wang, Shiyan</au><au>Lam, Cleo N. Y.</au><au>Feng, Hai</au><au>Zhao, Junhong</au><au>Cheng, Alfred S. L.</au><au>To, Ka‐Fai</au><au>Chan, Henry L. Y.</au><au>Sung, Joseph J. Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory role of peroxisome proliferator‐activated receptor gamma in hepatocarcinogenesis in mice and in vitro</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2010-06</date><risdate>2010</risdate><volume>51</volume><issue>6</issue><spage>2008</spage><epage>2019</epage><pages>2008-2019</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract><![CDATA[Although peroxisome proliferator‐activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ‐deficient (PPARγ+/−) and wild‐type (PPARγ+/+) littermates were used in a diethylnitrosamine (DEN)‐induced HCC model and treated with PPARγ agonist (rosiglitazone) or the vehicle alone for 8 months. The effects of PPARγ on HCC cell growth and apoptosis were examined using PPARγ‐expressing adenovirus (Ad‐PPARγ). PPARγ+/− mice were more susceptible to DEN‐induced HCC than PPARγ+/+ mice (94% versus 62%, P < 0.05), and rosiglitazone significantly reduced the incidence of HCC in PPARγ+/+ mice (vehicle 62% versus treatment 24%, P < 0.01), but not in PPARγ+/− mice, indicating that PPARγ suppresses hepatocellular carcinogenesis. A pronounced expression of PPARγ was observed in a HCC cell line (Hep3B) infected with Ad‐PPARγ. Such induction markedly suppressed HCC cell viability (P < 0.01). Further, Hep3B infection with Ad‐PPARγ revealed a decreased proportion of cells in S‐phase (12.92% versus 11.58%, P < 0.05), with arrest at G2/M phase (38.2% versus 55.68%, P < 0.001), and there was concomitant phosphorylation of the key G2/M phase inhibitors cdc25C and cdc2. PPARγ overexpression increased cell apoptosis (21.47% versus 35.02%, P < 0.01), mediated by both extrinsic (Fas and tumor necrosis factor‐α) and intrinsic (caspase‐9, caspase‐3, caspase‐7, and poly[ADP‐ribose] polymerase) pathways. Moreover, PPARγ directly induced a putative tumor suppressor gene, growth differentiation factor‐15. Conclusion: Loss of one PPARγ allele is sufficient to enhance susceptibility to HCC. PPARγ suppresses tumor cell growth through reducing cell proliferation and inducing G2/M phase arrest, apoptosis, and up‐regulating growth differentiation factor‐15. Thus, PPARγ acts as a tumor‐suppressor gene in the liver. HEPATOLOGY 2010]]></abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20512989</pmid><doi>10.1002/hep.23550</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviridae Adenovirus Alkylating Agents Animals Apoptosis Biological and medical sciences Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - prevention & control Cell Cycle Cell growth Cell Line, Tumor Cell Proliferation Diethylnitrosamine Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Profiling Genes Growth Differentiation Factor 15 - metabolism Hepatology Humans Hypoglycemic Agents - therapeutic use Liver Neoplasms, Experimental - genetics Liver Neoplasms, Experimental - metabolism Liver Neoplasms, Experimental - prevention & control Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Mice Mice, Knockout Oligonucleotide Array Sequence Analysis PPAR gamma - agonists PPAR gamma - genetics PPAR gamma - metabolism Thiazolidinediones - therapeutic use Tumors Up-Regulation |
| title | Inhibitory role of peroxisome proliferator‐activated receptor gamma in hepatocarcinogenesis in mice and in vitro |
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