Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target
Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targ...
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| Veröffentlicht in: | PloS one 2009-05, Vol.4 (5), p.e5565-e5565 |
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| creator | Montero, Juan Carlos Ocaña, Alberto Abad, Mar Ortiz-Ruiz, María Jesús Pandiella, Atanasio Esparís-Ogando, Azucena |
| description | Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK) play important roles in tumorigenesis. One of them, Erk5, has been linked to the proliferation of breast cancer cells in vitro. Here we have investigated the expression and prognostic value of Erk5 in human breast cancer.
Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5) was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5(AEF)), were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies.
Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target. |
| doi_str_mv | 10.1371/journal.pone.0005565 |
| format | Article |
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Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5) was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5(AEF)), were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies.
Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005565</identifier><identifier>PMID: 19440538</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Angiogenesis ; Animal models ; Animals ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Biochemistry/Cell Signaling and Trafficking Structures ; Blotting, Western ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - enzymology ; Cancer ; Care and treatment ; Cell Biology/Cell Growth and Division ; Cell Biology/Cell Signaling ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Correlation analysis ; Development and progression ; Disease-Free Survival ; Drug development ; Drugs ; Epidermal growth factor ; ErbB-2 protein ; Female ; Gene amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kinases ; Male ; MAP kinase ; Mathematical models ; Medical prognosis ; Medical treatment ; Metastasis ; Mice ; Middle Aged ; Mitogen-Activated Protein Kinase 7 - metabolism ; Mitogens ; Multiple myeloma ; Oncology/Breast Cancer ; Oxidative stress ; Patient outcomes ; Patients ; Prevention ; Prognosis ; Protein kinases ; Proteins ; Quinazolines - therapeutic use ; Receptor, ErbB-2 - antagonists & inhibitors ; Receptor, ErbB-2 - metabolism ; Ribonucleic acid ; RNA ; Rodents ; Signal transduction ; Survival ; Transfection ; Trastuzumab ; Tumorigenesis ; Tumors ; Western blotting ; Women's Health/Breast Cancer</subject><ispartof>PloS one, 2009-05, Vol.4 (5), p.e5565-e5565</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Montero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (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>Montero et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c690t-db926e457b47602a47541f1eaedd784bd0134fbb5434232244f60ed76387ec533</citedby><cites>FETCH-LOGICAL-c690t-db926e457b47602a47541f1eaedd784bd0134fbb5434232244f60ed76387ec533</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/PMC2678256/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678256/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19440538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montero, Juan Carlos</creatorcontrib><creatorcontrib>Ocaña, Alberto</creatorcontrib><creatorcontrib>Abad, Mar</creatorcontrib><creatorcontrib>Ortiz-Ruiz, María Jesús</creatorcontrib><creatorcontrib>Pandiella, Atanasio</creatorcontrib><creatorcontrib>Esparís-Ogando, Azucena</creatorcontrib><title>Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK) play important roles in tumorigenesis. One of them, Erk5, has been linked to the proliferation of breast cancer cells in vitro. Here we have investigated the expression and prognostic value of Erk5 in human breast cancer.
Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5) was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5(AEF)), were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies.
Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Biochemistry/Cell Signaling and Trafficking Structures</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - enzymology</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell Biology/Cell Growth and Division</subject><subject>Cell Biology/Cell Signaling</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Correlation analysis</subject><subject>Development and progression</subject><subject>Disease-Free Survival</subject><subject>Drug development</subject><subject>Drugs</subject><subject>Epidermal growth factor</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Gene amplification</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mathematical models</subject><subject>Medical prognosis</subject><subject>Medical treatment</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Mitogen-Activated Protein Kinase 7 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Montero, Juan Carlos</au><au>Ocaña, Alberto</au><au>Abad, Mar</au><au>Ortiz-Ruiz, María Jesús</au><au>Pandiella, Atanasio</au><au>Esparís-Ogando, Azucena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-05-15</date><risdate>2009</risdate><volume>4</volume><issue>5</issue><spage>e5565</spage><epage>e5565</epage><pages>e5565-e5565</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK) play important roles in tumorigenesis. One of them, Erk5, has been linked to the proliferation of breast cancer cells in vitro. Here we have investigated the expression and prognostic value of Erk5 in human breast cancer.
Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5) was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5(AEF)), were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies.
Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19440538</pmid><doi>10.1371/journal.pone.0005565</doi><tpages>e5565</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-05, Vol.4 (5), p.e5565-e5565 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289216244 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Aged, 80 and over Analysis Angiogenesis Animal models Animals Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized Antineoplastic Agents - therapeutic use Apoptosis Biochemistry/Cell Signaling and Trafficking Structures Blotting, Western Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - enzymology Cancer Care and treatment Cell Biology/Cell Growth and Division Cell Biology/Cell Signaling Cell growth Cell Line, Tumor Cell Proliferation Correlation analysis Development and progression Disease-Free Survival Drug development Drugs Epidermal growth factor ErbB-2 protein Female Gene amplification Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Kinases Male MAP kinase Mathematical models Medical prognosis Medical treatment Metastasis Mice Middle Aged Mitogen-Activated Protein Kinase 7 - metabolism Mitogens Multiple myeloma Oncology/Breast Cancer Oxidative stress Patient outcomes Patients Prevention Prognosis Protein kinases Proteins Quinazolines - therapeutic use Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Ribonucleic acid RNA Rodents Signal transduction Survival Transfection Trastuzumab Tumorigenesis Tumors Western blotting Women's Health/Breast Cancer |
| title | Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T09%3A44%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20of%20Erk5%20in%20early%20stage%20breast%20cancer%20and%20association%20with%20disease%20free%20survival%20identifies%20this%20kinase%20as%20a%20potential%20therapeutic%20target&rft.jtitle=PloS%20one&rft.au=Montero,%20Juan%20Carlos&rft.date=2009-05-15&rft.volume=4&rft.issue=5&rft.spage=e5565&rft.epage=e5565&rft.pages=e5565-e5565&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0005565&rft_dat=%3Cgale_plos_%3EA473154576%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289216244&rft_id=info:pmid/19440538&rft_galeid=A473154576&rft_doaj_id=oai_doaj_org_article_54878656132349f8b6aa66b08c130f59&rfr_iscdi=true |