Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer
Purpose: The Pygopus proteins are critical elements of the canonical Wnt/β-catenin transcriptional complex. In epithelial ovarian cancer, constitutively active Wnt signaling is restricted to one (endometrioid) tumor subtype. The purpose of this study was to determine the level of expression and grow...
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| Veröffentlicht in: | Clinical cancer research 2006-04, Vol.12 (7), p.2216-2223 |
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| creator | POPADIUK, Cathy M JIEYING XIONG WELLS, Malcolm G ANDREWS, Phillip G DANKWA, Kweku HIRASAWA, Kensuke LAKE, Blue B KAO, Kenneth R |
| description | Purpose: The Pygopus proteins are critical elements of the canonical Wnt/β-catenin transcriptional complex. In epithelial ovarian
cancer, constitutively active Wnt signaling is restricted to one (endometrioid) tumor subtype. The purpose of this study was
to determine the level of expression and growth requirements of human Pygopus2 (hPygo2) protein in epithelial ovarian cancer.
Experimental Design: Expression and subcellular localization of hPygo2 was determined in epithelial ovarian cancer cell lines and tumors using
Northern blot, immunoblot, and immunofluorescence. Immunohistochemistry was done on 125 archived patient epithelial ovarian
cancer tumors representing all epithelial ovarian cancer subtypes. T-cell factor–dependent transcription levels were determined
in epithelial ovarian cancer cells using TOPflash/FOPflash in vivo assays. Phosphorothioated antisense oligonucleotides were transfected into cell lines and growth assayed by cell counting,
anchorage-independent colony formation on soft agar, and xenografting into severe combined immunodeficient mice.
Results: All six epithelial ovarian cancer cell lines and 82% of the patient samples overexpressed nuclear hPygo2 compared with control
cells and benign disease. Depletion of hPygo2 by antisense oligonucleotides in both Wnt-active (TOV-112D) and Wnt-inactive
serous (OVCAR-3, SKOV-3) and clear cell (TOV-21G) carcinoma cell lines halted growth, assessed using tissue culture, anchorage-independent,
and xenograft assays.
Conclusions: hPygo2 is unexpectedly widely expressed in, and required in the absence of, Wnt signaling for malignant growth of epithelial
ovarian cancer, the deadliest gynecologic malignancy. These findings strongly suggest that inhibition of hPygo2 may be of
therapeutic benefit for treating this disease. |
| doi_str_mv | 10.1158/1078-0432.CCR-05-2433 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67854013</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20241294</sourcerecordid><originalsourceid>FETCH-LOGICAL-c566t-c7c33c2d37855a285556544f39390c2ddda21db698dfa3d3bcf57e10bf2f02213</originalsourceid><addsrcrecordid>eNqFkMtKxDAUhoMo3h9ByUZxU8097XIo4wUExQsuQyZNbKTT1qRVfHtTZ8SlmyQcvv-ckw-AI4zOMeb5BUYyzxCj5LwsHzLEM8Io3QC7mHOZUSL4Znr_MjtgL8Y3hDDDiG2DHSwEKhCVu-Bl1g4-2jZa-Dj2fbAx-q6FnYP3X69dP0YCH2wcmyFC38Kr0H0ONZyFxA0TNO_9UNvG6wbefejgdQtL3RobDsCW0020h-t7Hzxfzp_K6-z27uqmnN1mhgsxZEYaSg2pqMw51yQdXHDGHC1ogVK9qjTB1UIUeeU0rejCOC4tRgtHHCIE031wuurbh-59TFuppY_GNo1ubTdGJVJjhjD9FySIMEwKlkC-Ak3oYgzWqT74pQ5fCiM1qVeTVjVpVUm9QlxN6lPueD1gXCxt9Zdau07AyRrQ0ejGhSTKxz9OikKyvEjc2Yqr_Wv96YNV5kdpcm51MLXCREmVPi_oNwVkmeI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20241294</pqid></control><display><type>article</type><title>Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>POPADIUK, Cathy M ; JIEYING XIONG ; WELLS, Malcolm G ; ANDREWS, Phillip G ; DANKWA, Kweku ; HIRASAWA, Kensuke ; LAKE, Blue B ; KAO, Kenneth R</creator><creatorcontrib>POPADIUK, Cathy M ; JIEYING XIONG ; WELLS, Malcolm G ; ANDREWS, Phillip G ; DANKWA, Kweku ; HIRASAWA, Kensuke ; LAKE, Blue B ; KAO, Kenneth R</creatorcontrib><description>Purpose: The Pygopus proteins are critical elements of the canonical Wnt/β-catenin transcriptional complex. In epithelial ovarian
cancer, constitutively active Wnt signaling is restricted to one (endometrioid) tumor subtype. The purpose of this study was
to determine the level of expression and growth requirements of human Pygopus2 (hPygo2) protein in epithelial ovarian cancer.
Experimental Design: Expression and subcellular localization of hPygo2 was determined in epithelial ovarian cancer cell lines and tumors using
Northern blot, immunoblot, and immunofluorescence. Immunohistochemistry was done on 125 archived patient epithelial ovarian
cancer tumors representing all epithelial ovarian cancer subtypes. T-cell factor–dependent transcription levels were determined
in epithelial ovarian cancer cells using TOPflash/FOPflash in vivo assays. Phosphorothioated antisense oligonucleotides were transfected into cell lines and growth assayed by cell counting,
anchorage-independent colony formation on soft agar, and xenografting into severe combined immunodeficient mice.
Results: All six epithelial ovarian cancer cell lines and 82% of the patient samples overexpressed nuclear hPygo2 compared with control
cells and benign disease. Depletion of hPygo2 by antisense oligonucleotides in both Wnt-active (TOV-112D) and Wnt-inactive
serous (OVCAR-3, SKOV-3) and clear cell (TOV-21G) carcinoma cell lines halted growth, assessed using tissue culture, anchorage-independent,
and xenograft assays.
Conclusions: hPygo2 is unexpectedly widely expressed in, and required in the absence of, Wnt signaling for malignant growth of epithelial
ovarian cancer, the deadliest gynecologic malignancy. These findings strongly suggest that inhibition of hPygo2 may be of
therapeutic benefit for treating this disease.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-05-2433</identifier><identifier>PMID: 16609037</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; antisense knockdown ; Biological and medical sciences ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Disease Models, Animal ; Drug Screening Assays, Antitumor ; Epithelial Ovarian Cancer ; Female ; Female genital diseases ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - genetics ; Gynecology. Andrology. Obstetrics ; Humans ; In Vitro Techniques ; Intracellular Signaling Peptides and Proteins - drug effects ; Intracellular Signaling Peptides and Proteins - genetics ; Medical sciences ; Mice ; Neoplasms, Experimental - therapy ; Neoplasms, Glandular and Epithelial - drug therapy ; Oligodeoxyribonucleotides, Antisense - pharmacology ; Ovarian Neoplasms - drug therapy ; Pharmacology. Drug treatments ; Pygopus2 ; Structure-Activity Relationship ; Transplantation, Heterologous ; tumor inhibition ; Tumors ; Wnt transcription ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical cancer research, 2006-04, Vol.12 (7), p.2216-2223</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-c7c33c2d37855a285556544f39390c2ddda21db698dfa3d3bcf57e10bf2f02213</citedby><cites>FETCH-LOGICAL-c566t-c7c33c2d37855a285556544f39390c2ddda21db698dfa3d3bcf57e10bf2f02213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3354,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17697489$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16609037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>POPADIUK, Cathy M</creatorcontrib><creatorcontrib>JIEYING XIONG</creatorcontrib><creatorcontrib>WELLS, Malcolm G</creatorcontrib><creatorcontrib>ANDREWS, Phillip G</creatorcontrib><creatorcontrib>DANKWA, Kweku</creatorcontrib><creatorcontrib>HIRASAWA, Kensuke</creatorcontrib><creatorcontrib>LAKE, Blue B</creatorcontrib><creatorcontrib>KAO, Kenneth R</creatorcontrib><title>Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The Pygopus proteins are critical elements of the canonical Wnt/β-catenin transcriptional complex. In epithelial ovarian
cancer, constitutively active Wnt signaling is restricted to one (endometrioid) tumor subtype. The purpose of this study was
to determine the level of expression and growth requirements of human Pygopus2 (hPygo2) protein in epithelial ovarian cancer.
Experimental Design: Expression and subcellular localization of hPygo2 was determined in epithelial ovarian cancer cell lines and tumors using
Northern blot, immunoblot, and immunofluorescence. Immunohistochemistry was done on 125 archived patient epithelial ovarian
cancer tumors representing all epithelial ovarian cancer subtypes. T-cell factor–dependent transcription levels were determined
in epithelial ovarian cancer cells using TOPflash/FOPflash in vivo assays. Phosphorothioated antisense oligonucleotides were transfected into cell lines and growth assayed by cell counting,
anchorage-independent colony formation on soft agar, and xenografting into severe combined immunodeficient mice.
Results: All six epithelial ovarian cancer cell lines and 82% of the patient samples overexpressed nuclear hPygo2 compared with control
cells and benign disease. Depletion of hPygo2 by antisense oligonucleotides in both Wnt-active (TOV-112D) and Wnt-inactive
serous (OVCAR-3, SKOV-3) and clear cell (TOV-21G) carcinoma cell lines halted growth, assessed using tissue culture, anchorage-independent,
and xenograft assays.
Conclusions: hPygo2 is unexpectedly widely expressed in, and required in the absence of, Wnt signaling for malignant growth of epithelial
ovarian cancer, the deadliest gynecologic malignancy. These findings strongly suggest that inhibition of hPygo2 may be of
therapeutic benefit for treating this disease.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>antisense knockdown</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Disease Models, Animal</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Epithelial Ovarian Cancer</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Intracellular Signaling Peptides and Proteins - drug effects</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neoplasms, Experimental - therapy</subject><subject>Neoplasms, Glandular and Epithelial - drug therapy</subject><subject>Oligodeoxyribonucleotides, Antisense - pharmacology</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Pygopus2</subject><subject>Structure-Activity Relationship</subject><subject>Transplantation, Heterologous</subject><subject>tumor inhibition</subject><subject>Tumors</subject><subject>Wnt transcription</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKxDAUhoMo3h9ByUZxU8097XIo4wUExQsuQyZNbKTT1qRVfHtTZ8SlmyQcvv-ckw-AI4zOMeb5BUYyzxCj5LwsHzLEM8Io3QC7mHOZUSL4Znr_MjtgL8Y3hDDDiG2DHSwEKhCVu-Bl1g4-2jZa-Dj2fbAx-q6FnYP3X69dP0YCH2wcmyFC38Kr0H0ONZyFxA0TNO_9UNvG6wbefejgdQtL3RobDsCW0020h-t7Hzxfzp_K6-z27uqmnN1mhgsxZEYaSg2pqMw51yQdXHDGHC1ogVK9qjTB1UIUeeU0rejCOC4tRgtHHCIE031wuurbh-59TFuppY_GNo1ubTdGJVJjhjD9FySIMEwKlkC-Ak3oYgzWqT74pQ5fCiM1qVeTVjVpVUm9QlxN6lPueD1gXCxt9Zdau07AyRrQ0ejGhSTKxz9OikKyvEjc2Yqr_Wv96YNV5kdpcm51MLXCREmVPi_oNwVkmeI</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>POPADIUK, Cathy M</creator><creator>JIEYING XIONG</creator><creator>WELLS, Malcolm G</creator><creator>ANDREWS, Phillip G</creator><creator>DANKWA, Kweku</creator><creator>HIRASAWA, Kensuke</creator><creator>LAKE, Blue B</creator><creator>KAO, Kenneth R</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>7QO</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060401</creationdate><title>Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer</title><author>POPADIUK, Cathy M ; JIEYING XIONG ; WELLS, Malcolm G ; ANDREWS, Phillip G ; DANKWA, Kweku ; HIRASAWA, Kensuke ; LAKE, Blue B ; KAO, Kenneth R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-c7c33c2d37855a285556544f39390c2ddda21db698dfa3d3bcf57e10bf2f02213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>antisense knockdown</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Disease Models, Animal</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Epithelial Ovarian Cancer</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Intracellular Signaling Peptides and Proteins - drug effects</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neoplasms, Experimental - therapy</topic><topic>Neoplasms, Glandular and Epithelial - drug therapy</topic><topic>Oligodeoxyribonucleotides, Antisense - pharmacology</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Pygopus2</topic><topic>Structure-Activity Relationship</topic><topic>Transplantation, Heterologous</topic><topic>tumor inhibition</topic><topic>Tumors</topic><topic>Wnt transcription</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>POPADIUK, Cathy M</creatorcontrib><creatorcontrib>JIEYING XIONG</creatorcontrib><creatorcontrib>WELLS, Malcolm G</creatorcontrib><creatorcontrib>ANDREWS, Phillip G</creatorcontrib><creatorcontrib>DANKWA, Kweku</creatorcontrib><creatorcontrib>HIRASAWA, Kensuke</creatorcontrib><creatorcontrib>LAKE, Blue B</creatorcontrib><creatorcontrib>KAO, Kenneth R</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>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>POPADIUK, Cathy M</au><au>JIEYING XIONG</au><au>WELLS, Malcolm G</au><au>ANDREWS, Phillip G</au><au>DANKWA, Kweku</au><au>HIRASAWA, Kensuke</au><au>LAKE, Blue B</au><au>KAO, Kenneth R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>12</volume><issue>7</issue><spage>2216</spage><epage>2223</epage><pages>2216-2223</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The Pygopus proteins are critical elements of the canonical Wnt/β-catenin transcriptional complex. In epithelial ovarian
cancer, constitutively active Wnt signaling is restricted to one (endometrioid) tumor subtype. The purpose of this study was
to determine the level of expression and growth requirements of human Pygopus2 (hPygo2) protein in epithelial ovarian cancer.
Experimental Design: Expression and subcellular localization of hPygo2 was determined in epithelial ovarian cancer cell lines and tumors using
Northern blot, immunoblot, and immunofluorescence. Immunohistochemistry was done on 125 archived patient epithelial ovarian
cancer tumors representing all epithelial ovarian cancer subtypes. T-cell factor–dependent transcription levels were determined
in epithelial ovarian cancer cells using TOPflash/FOPflash in vivo assays. Phosphorothioated antisense oligonucleotides were transfected into cell lines and growth assayed by cell counting,
anchorage-independent colony formation on soft agar, and xenografting into severe combined immunodeficient mice.
Results: All six epithelial ovarian cancer cell lines and 82% of the patient samples overexpressed nuclear hPygo2 compared with control
cells and benign disease. Depletion of hPygo2 by antisense oligonucleotides in both Wnt-active (TOV-112D) and Wnt-inactive
serous (OVCAR-3, SKOV-3) and clear cell (TOV-21G) carcinoma cell lines halted growth, assessed using tissue culture, anchorage-independent,
and xenograft assays.
Conclusions: hPygo2 is unexpectedly widely expressed in, and required in the absence of, Wnt signaling for malignant growth of epithelial
ovarian cancer, the deadliest gynecologic malignancy. These findings strongly suggest that inhibition of hPygo2 may be of
therapeutic benefit for treating this disease.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16609037</pmid><doi>10.1158/1078-0432.CCR-05-2433</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2006-04, Vol.12 (7), p.2216-2223 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic agents antisense knockdown Biological and medical sciences Cell Line, Tumor Cell Proliferation - drug effects Disease Models, Animal Drug Screening Assays, Antitumor Epithelial Ovarian Cancer Female Female genital diseases Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - genetics Gynecology. Andrology. Obstetrics Humans In Vitro Techniques Intracellular Signaling Peptides and Proteins - drug effects Intracellular Signaling Peptides and Proteins - genetics Medical sciences Mice Neoplasms, Experimental - therapy Neoplasms, Glandular and Epithelial - drug therapy Oligodeoxyribonucleotides, Antisense - pharmacology Ovarian Neoplasms - drug therapy Pharmacology. Drug treatments Pygopus2 Structure-Activity Relationship Transplantation, Heterologous tumor inhibition Tumors Wnt transcription Xenograft Model Antitumor Assays |
| title | Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer |
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