Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy
Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42...
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| description | Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), cultures were treated with the PPARγ ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPARγ antagonist. Taken together, these studies show PTEN–cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPARγ ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency. |
| doi_str_mv | 10.1038/onc.2012.140 |
| format | Article |
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Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), cultures were treated with the PPARγ ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPARγ antagonist. Taken together, these studies show PTEN–cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPARγ ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2012.140</identifier><identifier>PMID: 22543585</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 631/136/1660 ; 631/67/1059/602 ; 631/67/1504/1885 ; Anilides - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Benign ; Caco-2 Cells ; Cancer ; Care and treatment ; cdc42 GTP-Binding Protein - metabolism ; Cdc42 protein ; Cell activation ; Cell Biology ; Cell culture ; Cell division ; Cell Growth Processes - drug effects ; Cell Growth Processes - physiology ; Cell size ; Chromosomes ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Development ; Epithelium ; Genetic aspects ; Glands ; Guanine ; Guanine nucleotide exchange factor ; Guanosinetriphosphatase ; HCT116 Cells ; Health aspects ; Human Genetics ; Humans ; Internal Medicine ; Ligands ; Localization ; Madin Darby Canine Kidney Cells ; Medicine ; Medicine & Public Health ; Molecular Targeted Therapy ; Morphogenesis ; Nuclear receptors ; Oncology ; original-article ; Peroxisome proliferator-activated receptors ; Phenotypes ; PPAR gamma - antagonists & inhibitors ; PPAR gamma - genetics ; PPAR gamma - metabolism ; PTEN Phosphohydrolase - deficiency ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; RNA ; Rosiglitazone ; Signal Transduction ; Tensin ; Thiazolidinediones - pharmacology ; Transfection ; Vacuoles</subject><ispartof>Oncogene, 2013-03, Vol.32 (10), p.1305-1315</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2013.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-4cdc61ae526bda8fa4838e2a23ca1da3742a5cc0a90e7334836a672a86ca5a503</citedby><cites>FETCH-LOGICAL-c550t-4cdc61ae526bda8fa4838e2a23ca1da3742a5cc0a90e7334836a672a86ca5a503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2012.140$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2012.140$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22543585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jagan, I</creatorcontrib><creatorcontrib>Fatehullah, A</creatorcontrib><creatorcontrib>Deevi, R K</creatorcontrib><creatorcontrib>Bingham, V</creatorcontrib><creatorcontrib>Campbell, F C</creatorcontrib><title>Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), cultures were treated with the PPARγ ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPARγ antagonist. Taken together, these studies show PTEN–cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPARγ ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>631/136/1660</subject><subject>631/67/1059/602</subject><subject>631/67/1504/1885</subject><subject>Anilides - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Benign</subject><subject>Caco-2 Cells</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>cdc42 GTP-Binding Protein - metabolism</subject><subject>Cdc42 protein</subject><subject>Cell activation</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell division</subject><subject>Cell Growth Processes - drug effects</subject><subject>Cell Growth Processes - physiology</subject><subject>Cell size</subject><subject>Chromosomes</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development</subject><subject>Epithelium</subject><subject>Genetic aspects</subject><subject>Glands</subject><subject>Guanine</subject><subject>Guanine nucleotide exchange factor</subject><subject>Guanosinetriphosphatase</subject><subject>HCT116 Cells</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Ligands</subject><subject>Localization</subject><subject>Madin Darby Canine Kidney Cells</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular Targeted Therapy</subject><subject>Morphogenesis</subject><subject>Nuclear receptors</subject><subject>Oncology</subject><subject>original-article</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Phenotypes</subject><subject>PPAR gamma - antagonists & inhibitors</subject><subject>PPAR gamma - genetics</subject><subject>PPAR gamma - metabolism</subject><subject>PTEN Phosphohydrolase - deficiency</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>RNA</subject><subject>Rosiglitazone</subject><subject>Signal Transduction</subject><subject>Tensin</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Transfection</subject><subject>Vacuoles</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNks1u1DAUhSMEokNhxxpZYsOCDP5PZoM0qsqPVMGoKmvrjnOTcZXYwU6Q5rl4D54Jj6a0FHWBvLDk-92j63NPUbxkdMmoqN8Fb5ecMr5kkj4qFkxWulRqJR8XC7pStFxxwU-KZyldU0qrFeVPixPOlRSqVovCX2KyM5LQkq4H38w9RNLs0xDiuAsdekwuEefJ5ur8S9lg66xDPxEb-hDRTtATC95iJDi6aYe9mwey3ZPNZn3562c5QexwwobkUoRx_7x40kKf8MXNfVp8-3B-dfapvPj68fPZ-qK0StGplLaxmgEqrrcN1C3IWtTIgQsLrAFRSQ7KWgoripUQuapBVxxqbUGBouK0eH_UHeftgI3NI0fozRjdAHFvAjhzv-LdznThhxFS6lqrLPDmRiCG7zOmyQwuWeyzRxjmZJjgoqZKc_kfKMtcXoPO6Ot_0OswR5-dMFxLplhm2B3VQY_G-TbkEe1B1KxFXp0WuhaZWj5A5dPg4GzweVX5_V7D22ODjSGliO2tHYyaQ5RMjpI5RMnkKGX81d8W3sJ_spOB8gikXPIdxrvPPCj4G0M708g</recordid><startdate>20130307</startdate><enddate>20130307</enddate><creator>Jagan, I</creator><creator>Fatehullah, A</creator><creator>Deevi, R K</creator><creator>Bingham, V</creator><creator>Campbell, F C</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130307</creationdate><title>Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy</title><author>Jagan, I ; Fatehullah, A ; Deevi, R K ; Bingham, V ; Campbell, F C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-4cdc61ae526bda8fa4838e2a23ca1da3742a5cc0a90e7334836a672a86ca5a503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>631/136/1660</topic><topic>631/67/1059/602</topic><topic>631/67/1504/1885</topic><topic>Anilides - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Benign</topic><topic>Caco-2 Cells</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>cdc42 GTP-Binding Protein - metabolism</topic><topic>Cdc42 protein</topic><topic>Cell activation</topic><topic>Cell Biology</topic><topic>Cell culture</topic><topic>Cell division</topic><topic>Cell Growth Processes - drug effects</topic><topic>Cell Growth Processes - physiology</topic><topic>Cell size</topic><topic>Chromosomes</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Development</topic><topic>Epithelium</topic><topic>Genetic aspects</topic><topic>Glands</topic><topic>Guanine</topic><topic>Guanine nucleotide exchange factor</topic><topic>Guanosinetriphosphatase</topic><topic>HCT116 Cells</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Ligands</topic><topic>Localization</topic><topic>Madin Darby Canine Kidney Cells</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular Targeted Therapy</topic><topic>Morphogenesis</topic><topic>Nuclear receptors</topic><topic>Oncology</topic><topic>original-article</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Phenotypes</topic><topic>PPAR gamma - antagonists & inhibitors</topic><topic>PPAR gamma - genetics</topic><topic>PPAR gamma - metabolism</topic><topic>PTEN Phosphohydrolase - deficiency</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>RNA</topic><topic>Rosiglitazone</topic><topic>Signal Transduction</topic><topic>Tensin</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Transfection</topic><topic>Vacuoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jagan, I</creatorcontrib><creatorcontrib>Fatehullah, A</creatorcontrib><creatorcontrib>Deevi, R K</creatorcontrib><creatorcontrib>Bingham, V</creatorcontrib><creatorcontrib>Campbell, F C</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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>Research Library (Alumni Edition)</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jagan, I</au><au>Fatehullah, A</au><au>Deevi, R K</au><au>Bingham, V</au><au>Campbell, F C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2013-03-07</date><risdate>2013</risdate><volume>32</volume><issue>10</issue><spage>1305</spage><epage>1315</epage><pages>1305-1315</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), cultures were treated with the PPARγ ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPARγ antagonist. Taken together, these studies show PTEN–cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPARγ ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22543585</pmid><doi>10.1038/onc.2012.140</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2013-03, Vol.32 (10), p.1305-1315 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3446865 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 1-Phosphatidylinositol 3-kinase 631/136/1660 631/67/1059/602 631/67/1504/1885 Anilides - pharmacology Apoptosis Apoptosis - drug effects Apoptosis - physiology Benign Caco-2 Cells Cancer Care and treatment cdc42 GTP-Binding Protein - metabolism Cdc42 protein Cell activation Cell Biology Cell culture Cell division Cell Growth Processes - drug effects Cell Growth Processes - physiology Cell size Chromosomes Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Development Epithelium Genetic aspects Glands Guanine Guanine nucleotide exchange factor Guanosinetriphosphatase HCT116 Cells Health aspects Human Genetics Humans Internal Medicine Ligands Localization Madin Darby Canine Kidney Cells Medicine Medicine & Public Health Molecular Targeted Therapy Morphogenesis Nuclear receptors Oncology original-article Peroxisome proliferator-activated receptors Phenotypes PPAR gamma - antagonists & inhibitors PPAR gamma - genetics PPAR gamma - metabolism PTEN Phosphohydrolase - deficiency PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein RNA Rosiglitazone Signal Transduction Tensin Thiazolidinediones - pharmacology Transfection Vacuoles |
| title | Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T18%3A41%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rescue%20of%20glandular%20dysmorphogenesis%20in%20PTEN-deficient%20colorectal%20cancer%20epithelium%20by%20PPAR%CE%B3-targeted%20therapy&rft.jtitle=Oncogene&rft.au=Jagan,%20I&rft.date=2013-03-07&rft.volume=32&rft.issue=10&rft.spage=1305&rft.epage=1315&rft.pages=1305-1315&rft.issn=0950-9232&rft.eissn=1476-5594&rft_id=info:doi/10.1038/onc.2012.140&rft_dat=%3Cgale_pubme%3EA322563683%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2641513631&rft_id=info:pmid/22543585&rft_galeid=A322563683&rfr_iscdi=true |