Targets of Wnt/ß-catenin transcription in penile carcinoma
Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disea...
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| Veröffentlicht in: | PloS one 2015, Vol.10 (4), p.e0124395 |
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| creator | Arya, Manit Thrasivoulou, Christopher Henrique, Rui Millar, Michael Hamblin, Ruth Davda, Reena Aare, Kristina Masters, John R Thomson, Calum Muneer, Asif Patel, Hitendra R H Ahmed, Aamir |
| description | Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p |
| doi_str_mv | 10.1371/journal.pone.0124395 |
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The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0124395</identifier><identifier>PMID: 25901368</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antigens, CD1 - metabolism ; Arrays ; Basale biofag: 470 ; beta Catenin - genetics ; beta Catenin - metabolism ; Biomarkers ; c-Myc protein ; Cancer ; Carcinogenesis ; Carcinogens ; Case-Control Studies ; Catenin ; Cell cycle ; Cellebiologi: 471 ; Combinations (mathematics) ; Disease ; Gene Expression Regulation, Neoplastic ; Genes ; Genital cancers ; Heparan sulfate ; Hospitals ; Humans ; Immunohistochemistry ; Klinisk medisinske fag: 750 ; Localization ; Male ; Malignancy ; Matematikk og Naturvitenskap: 400 ; Matrilysin ; Matrix Metalloproteinase 7 - metabolism ; Medical research ; Medisinske Fag: 700 ; Molecular modelling ; Mutation ; Myc protein ; Neoplasm Grading ; Neoplasm Proteins - metabolism ; Onkologi: 762 ; Penile Neoplasms - genetics ; Penile Neoplasms - pathology ; Penis ; Permutations ; Prostate cancer ; Proteins ; Proto-Oncogene Proteins c-myc - metabolism ; Signal transduction ; Signaling ; Squamous cell carcinoma ; Surgery ; Tissues ; Transcription activation ; Transcription, Genetic ; Tumors ; Urology ; VDP ; Wnt protein ; Wnt4 Protein - genetics ; Wnt4 Protein - metabolism ; Womens health</subject><ispartof>PloS one, 2015, Vol.10 (4), p.e0124395</ispartof><rights>2015 Arya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>2015 Arya et al 2015 Arya et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3945-72ec1f291d9375b2f67ed93d4453109ac80925c5ba723cb4e081936571bdca673</citedby><cites>FETCH-LOGICAL-c3945-72ec1f291d9375b2f67ed93d4453109ac80925c5ba723cb4e081936571bdca673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406530/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406530/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,4024,23866,26567,27923,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25901368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Toland, Amanda Ewart</contributor><creatorcontrib>Arya, Manit</creatorcontrib><creatorcontrib>Thrasivoulou, Christopher</creatorcontrib><creatorcontrib>Henrique, Rui</creatorcontrib><creatorcontrib>Millar, Michael</creatorcontrib><creatorcontrib>Hamblin, Ruth</creatorcontrib><creatorcontrib>Davda, Reena</creatorcontrib><creatorcontrib>Aare, Kristina</creatorcontrib><creatorcontrib>Masters, John R</creatorcontrib><creatorcontrib>Thomson, Calum</creatorcontrib><creatorcontrib>Muneer, Asif</creatorcontrib><creatorcontrib>Patel, Hitendra R H</creatorcontrib><creatorcontrib>Ahmed, Aamir</creatorcontrib><title>Targets of Wnt/ß-catenin transcription in penile carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.</description><subject>Antigens, CD1 - metabolism</subject><subject>Arrays</subject><subject>Basale biofag: 470</subject><subject>beta Catenin - genetics</subject><subject>beta Catenin - metabolism</subject><subject>Biomarkers</subject><subject>c-Myc protein</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Case-Control Studies</subject><subject>Catenin</subject><subject>Cell cycle</subject><subject>Cellebiologi: 471</subject><subject>Combinations (mathematics)</subject><subject>Disease</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genital cancers</subject><subject>Heparan sulfate</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Klinisk medisinske fag: 750</subject><subject>Localization</subject><subject>Male</subject><subject>Malignancy</subject><subject>Matematikk og Naturvitenskap: 400</subject><subject>Matrilysin</subject><subject>Matrix Metalloproteinase 7 - metabolism</subject><subject>Medical research</subject><subject>Medisinske Fag: 700</subject><subject>Molecular modelling</subject><subject>Mutation</subject><subject>Myc protein</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Onkologi: 762</subject><subject>Penile Neoplasms - genetics</subject><subject>Penile Neoplasms - pathology</subject><subject>Penis</subject><subject>Permutations</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Squamous cell carcinoma</subject><subject>Surgery</subject><subject>Tissues</subject><subject>Transcription activation</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><subject>Urology</subject><subject>VDP</subject><subject>Wnt protein</subject><subject>Wnt4 Protein - genetics</subject><subject>Wnt4 Protein - metabolism</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>3HK</sourceid><sourceid>DOA</sourceid><recordid>eNp1Ustq3DAUFaWlSab9g5IYuvZEb1kECiU0Dwhkk9KluJblqQaP5EieQr-mH9Mfq5LxJM0iK13u45xzjy5CnwheEqbI6TpuU4BhOcbglphQzrR4gw6JZrSWFLO3_8UH6CjnNcaCNVK-RwdUaEyYbA7R2R2klZtyFfvqR5hO__6pLUwu-FBNCUK2yY-Tj6EqibGkB1dZSNaHuIEP6F0PQ3Yf53eBvl98uzu_qm9uL6_Pv97UlmkuakWdJT3VpNNMiZb2UrkSdpwLRrAG22BNhRUtKMpsyx1uinApFGk7C1KxBTrZ4Y5DzGbeOxsiFdcNJVqWjutdRxdhbcbkN5B-mwjePCZiWhlIk7eDMxpb3hf_WM8xL2qANKB53wloKesoK1hfZrZtu3GddaEYMbwAfVkJ_qdZxV-GcywFwwXgeAdQvMuTDybEBIZgzJTRsvi-QJ9nhhTvty5Pr-zE9zAx5-T6JwkEm4cL2E-Zhwsw8wU8s-9EPg3tv5z9A4mSrQU</recordid><startdate>2015</startdate><enddate>2015</enddate><creator>Arya, Manit</creator><creator>Thrasivoulou, Christopher</creator><creator>Henrique, Rui</creator><creator>Millar, Michael</creator><creator>Hamblin, Ruth</creator><creator>Davda, Reena</creator><creator>Aare, Kristina</creator><creator>Masters, John R</creator><creator>Thomson, Calum</creator><creator>Muneer, Asif</creator><creator>Patel, Hitendra R H</creator><creator>Ahmed, Aamir</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>3HK</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>2015</creationdate><title>Targets of Wnt/ß-catenin transcription in penile carcinoma</title><author>Arya, Manit ; Thrasivoulou, Christopher ; Henrique, Rui ; Millar, Michael ; Hamblin, Ruth ; Davda, Reena ; Aare, Kristina ; Masters, John R ; Thomson, Calum ; Muneer, Asif ; Patel, Hitendra R H ; Ahmed, Aamir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3945-72ec1f291d9375b2f67ed93d4453109ac80925c5ba723cb4e081936571bdca673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antigens, CD1 - 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The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. 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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015, Vol.10 (4), p.e0124395 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1674982196 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Antigens, CD1 - metabolism Arrays Basale biofag: 470 beta Catenin - genetics beta Catenin - metabolism Biomarkers c-Myc protein Cancer Carcinogenesis Carcinogens Case-Control Studies Catenin Cell cycle Cellebiologi: 471 Combinations (mathematics) Disease Gene Expression Regulation, Neoplastic Genes Genital cancers Heparan sulfate Hospitals Humans Immunohistochemistry Klinisk medisinske fag: 750 Localization Male Malignancy Matematikk og Naturvitenskap: 400 Matrilysin Matrix Metalloproteinase 7 - metabolism Medical research Medisinske Fag: 700 Molecular modelling Mutation Myc protein Neoplasm Grading Neoplasm Proteins - metabolism Onkologi: 762 Penile Neoplasms - genetics Penile Neoplasms - pathology Penis Permutations Prostate cancer Proteins Proto-Oncogene Proteins c-myc - metabolism Signal transduction Signaling Squamous cell carcinoma Surgery Tissues Transcription activation Transcription, Genetic Tumors Urology VDP Wnt protein Wnt4 Protein - genetics Wnt4 Protein - metabolism Womens health |
| title | Targets of Wnt/ß-catenin transcription in penile carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T07%3A33%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targets%20of%20Wnt/%C3%9F-catenin%20transcription%20in%20penile%20carcinoma&rft.jtitle=PloS%20one&rft.au=Arya,%20Manit&rft.date=2015&rft.volume=10&rft.issue=4&rft.spage=e0124395&rft.pages=e0124395-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0124395&rft_dat=%3Cproquest_plos_%3E3662996221%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1674982196&rft_id=info:pmid/25901368&rft_doaj_id=oai_doaj_org_article_90c4f3713f4045b2a18a94fd5ab23d23&rfr_iscdi=true |