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Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer
Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its cognate ligand. Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR and Western...
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| Published in: | Clinical cancer research 2008-09, Vol.14 (17), p.5332-5340 |
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| Main Authors: | , , , , , , , , |
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| container_end_page | 5340 |
| container_issue | 17 |
| container_start_page | 5332 |
| container_title | Clinical cancer research |
| container_volume | 14 |
| creator | GUPTA, Divya VENKATESH, Madhukumar HONGWEI WANG KIM, Sean SINZ, Michael GOLDBERG, Gary L WHITNEY, Kathleen LONGLEY, Clifford MANI, Sridhar |
| description | Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its
cognate ligand.
Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR
and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)–induced
PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed
by MTT assay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts.
Results: PXR is expressed in ovarian cancer cells. In SKOV-3 cells, PXR is functional and its activation by cognate ligands induces
PXR target genes (CYP2B6, CYP3A4, and UGT1A1) but not MDR1 and MRP2. PXR activation in SKOV-3 cells induces cell proliferation
and drug resistance. In mice harboring SKOV-3 xenografts, rifampicin (PXR agonist) induces cell proliferation and tumor growth.
Conclusion: PXR activation, regardless of the type of ligand agonist present, promotes the “malignant” phenotype of cancer cells. These
data serve as the basis for finding novel nontoxic inhibitors of PXR activation as a method to control cell growth and prevent
induction of drug resistance. |
| doi_str_mv | 10.1158/1078-0432.CCR-08-1033 |
| format | article |
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cognate ligand.
Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR
and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)–induced
PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed
by MTT assay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts.
Results: PXR is expressed in ovarian cancer cells. In SKOV-3 cells, PXR is functional and its activation by cognate ligands induces
PXR target genes (CYP2B6, CYP3A4, and UGT1A1) but not MDR1 and MRP2. PXR activation in SKOV-3 cells induces cell proliferation
and drug resistance. In mice harboring SKOV-3 xenografts, rifampicin (PXR agonist) induces cell proliferation and tumor growth.
Conclusion: PXR activation, regardless of the type of ligand agonist present, promotes the “malignant” phenotype of cancer cells. These
data serve as the basis for finding novel nontoxic inhibitors of PXR activation as a method to control cell growth and prevent
induction of drug resistance.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-08-1033</identifier><identifier>PMID: 18765524</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Multiple - genetics ; Drug Resistance, Neoplasm - genetics ; Female ; Female genital diseases ; Gynecology. Andrology. Obstetrics ; Humans ; Ligands ; Medical sciences ; metabolism ; Mice ; Mice, Inbred NOD ; nuclear receptor ; ovarian cancer ; Ovarian Neoplasms - genetics ; Pharmacology. Drug treatments ; PXR ; Receptors, Steroid - genetics ; Transcriptional Activation ; Tumors</subject><ispartof>Clinical cancer research, 2008-09, Vol.14 (17), p.5332-5340</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-19decaaa2e73754b383c3611afe8537b532f6ad4b60c697c545cfb92b1c799783</citedby><cites>FETCH-LOGICAL-c536t-19decaaa2e73754b383c3611afe8537b532f6ad4b60c697c545cfb92b1c799783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20971289$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18765524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GUPTA, Divya</creatorcontrib><creatorcontrib>VENKATESH, Madhukumar</creatorcontrib><creatorcontrib>HONGWEI WANG</creatorcontrib><creatorcontrib>KIM, Sean</creatorcontrib><creatorcontrib>SINZ, Michael</creatorcontrib><creatorcontrib>GOLDBERG, Gary L</creatorcontrib><creatorcontrib>WHITNEY, Kathleen</creatorcontrib><creatorcontrib>LONGLEY, Clifford</creatorcontrib><creatorcontrib>MANI, Sridhar</creatorcontrib><title>Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its
cognate ligand.
Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR
and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)–induced
PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed
by MTT assay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts.
Results: PXR is expressed in ovarian cancer cells. In SKOV-3 cells, PXR is functional and its activation by cognate ligands induces
PXR target genes (CYP2B6, CYP3A4, and UGT1A1) but not MDR1 and MRP2. PXR activation in SKOV-3 cells induces cell proliferation
and drug resistance. In mice harboring SKOV-3 xenografts, rifampicin (PXR agonist) induces cell proliferation and tumor growth.
Conclusion: PXR activation, regardless of the type of ligand agonist present, promotes the “malignant” phenotype of cancer cells. These
data serve as the basis for finding novel nontoxic inhibitors of PXR activation as a method to control cell growth and prevent
induction of drug resistance.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Drug Resistance, Multiple - genetics</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>metabolism</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>nuclear receptor</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Pharmacology. Drug treatments</subject><subject>PXR</subject><subject>Receptors, Steroid - genetics</subject><subject>Transcriptional Activation</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNpFkE1v1DAQhi0EoqXwE0C-gMQhxeOx45hbFcqHVKloBRI3y_FOdl1lk8XO8vHvcdgtnGY0ft6x5mHsOYhLAN28AWGaSiiUl227qkRTgUB8wM5Ba1OhrPXD0t8zZ-xJzndCgAKhHrMzaEyttVTn7O76196P6zhu-LwlvpoGyryfEv-caDP6kfg3vqJA-7nM4shbPwZKb8vzNMSekp_jNPKygb9Lh01Bc8zzwizw7Q-for8PPWWPej9kenaqF-zr--sv7cfq5vbDp_bqpgoa67kCu6bgvZdk0GjVYYMBawDfU6PRdBplX_u16moRamuCVjr0nZUdBGOtafCCvTru3afp-4Hy7HYxBxqGcs10yK62ygqpVQH1EQxpyjlR7_Yp7nz67UC4RbJbBLpFoCuSnVgGiCX34vTBodvR-n_qZLUAL0-Az8EPfSr3x_yPk8IakI0t3Osjt42b7c-YyIW_phJl8ilsHSgHxmlEiX8AuLWS9w</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>GUPTA, Divya</creator><creator>VENKATESH, Madhukumar</creator><creator>HONGWEI WANG</creator><creator>KIM, Sean</creator><creator>SINZ, Michael</creator><creator>GOLDBERG, Gary L</creator><creator>WHITNEY, Kathleen</creator><creator>LONGLEY, Clifford</creator><creator>MANI, Sridhar</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>20080901</creationdate><title>Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer</title><author>GUPTA, Divya ; VENKATESH, Madhukumar ; HONGWEI WANG ; KIM, Sean ; SINZ, Michael ; GOLDBERG, Gary L ; WHITNEY, Kathleen ; LONGLEY, Clifford ; MANI, Sridhar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-19decaaa2e73754b383c3611afe8537b532f6ad4b60c697c545cfb92b1c799783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Drug Resistance, Multiple - genetics</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>metabolism</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>nuclear receptor</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Pharmacology. Drug treatments</topic><topic>PXR</topic><topic>Receptors, Steroid - genetics</topic><topic>Transcriptional Activation</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GUPTA, Divya</creatorcontrib><creatorcontrib>VENKATESH, Madhukumar</creatorcontrib><creatorcontrib>HONGWEI WANG</creatorcontrib><creatorcontrib>KIM, Sean</creatorcontrib><creatorcontrib>SINZ, Michael</creatorcontrib><creatorcontrib>GOLDBERG, Gary L</creatorcontrib><creatorcontrib>WHITNEY, Kathleen</creatorcontrib><creatorcontrib>LONGLEY, Clifford</creatorcontrib><creatorcontrib>MANI, Sridhar</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>GUPTA, Divya</au><au>VENKATESH, Madhukumar</au><au>HONGWEI WANG</au><au>KIM, Sean</au><au>SINZ, Michael</au><au>GOLDBERG, Gary L</au><au>WHITNEY, Kathleen</au><au>LONGLEY, Clifford</au><au>MANI, Sridhar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>14</volume><issue>17</issue><spage>5332</spage><epage>5340</epage><pages>5332-5340</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its
cognate ligand.
Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR
and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)–induced
PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed
by MTT assay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts.
Results: PXR is expressed in ovarian cancer cells. In SKOV-3 cells, PXR is functional and its activation by cognate ligands induces
PXR target genes (CYP2B6, CYP3A4, and UGT1A1) but not MDR1 and MRP2. PXR activation in SKOV-3 cells induces cell proliferation
and drug resistance. In mice harboring SKOV-3 xenografts, rifampicin (PXR agonist) induces cell proliferation and tumor growth.
Conclusion: PXR activation, regardless of the type of ligand agonist present, promotes the “malignant” phenotype of cancer cells. These
data serve as the basis for finding novel nontoxic inhibitors of PXR activation as a method to control cell growth and prevent
induction of drug resistance.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18765524</pmid><doi>10.1158/1078-0432.CCR-08-1033</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2008-09, Vol.14 (17), p.5332-5340 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | Freely Accessible Science Journals |
| subjects | Animals Antineoplastic agents Biological and medical sciences Cell Line, Tumor Cell Proliferation Drug Resistance, Multiple - genetics Drug Resistance, Neoplasm - genetics Female Female genital diseases Gynecology. Andrology. Obstetrics Humans Ligands Medical sciences metabolism Mice Mice, Inbred NOD nuclear receptor ovarian cancer Ovarian Neoplasms - genetics Pharmacology. Drug treatments PXR Receptors, Steroid - genetics Transcriptional Activation Tumors |
| title | Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer |
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