Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway
Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fib...
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Veröffentlicht in: | Human reproduction (Oxford) 2007, Vol.22 (1), p.36-44 |
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creator | Battersby, S. Sales, K.J. Williams, A.R. Anderson, R.A. Gardner, S. Jabbour, H.N. |
description | Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo. |
doi_str_mv | 10.1093/humrep/del328 |
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Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/del328</identifier><identifier>PMID: 16905765</identifier><identifier>CODEN: HUREEE</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adenocarcinoma - metabolism ; Biological and medical sciences ; Cell Line, Tumor ; Cyclic AMP - metabolism ; Dinoprostone - physiology ; Endometrial Neoplasms - metabolism ; ErbB Receptors - physiology ; Extracellular Signal-Regulated MAP Kinases - physiology ; Female ; Fibroblast Growth Factor 2 - biosynthesis ; Gene Expression Regulation ; Gynecology. Andrology. Obstetrics ; Humans ; Male ; Medical sciences ; Microscopy, Confocal ; Microscopy, Fluorescence ; Phosphorylation - drug effects ; Proto-Oncogene Proteins pp60(c-src) - metabolism ; Receptors, Prostaglandin E - physiology ; Receptors, Prostaglandin E, EP2 Subtype ; Semen - physiology ; Signal Transduction ; Transcriptional Activation - physiology ; Up-Regulation</subject><ispartof>Human reproduction (Oxford), 2007, Vol.22 (1), p.36-44</ispartof><rights>The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2007</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Jan 2007</rights><rights>The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</citedby><cites>FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18583687$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16905765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Battersby, S.</creatorcontrib><creatorcontrib>Sales, K.J.</creatorcontrib><creatorcontrib>Williams, A.R.</creatorcontrib><creatorcontrib>Anderson, R.A.</creatorcontrib><creatorcontrib>Gardner, S.</creatorcontrib><creatorcontrib>Jabbour, H.N.</creatorcontrib><title>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><addtitle>Hum Reprod</addtitle><description>Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</description><subject>Adenocarcinoma - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cyclic AMP - metabolism</subject><subject>Dinoprostone - physiology</subject><subject>Endometrial Neoplasms - metabolism</subject><subject>ErbB Receptors - physiology</subject><subject>Extracellular Signal-Regulated MAP Kinases - physiology</subject><subject>Female</subject><subject>Fibroblast Growth Factor 2 - biosynthesis</subject><subject>Gene Expression Regulation</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Phosphorylation - drug effects</subject><subject>Proto-Oncogene Proteins pp60(c-src) - metabolism</subject><subject>Receptors, Prostaglandin E - physiology</subject><subject>Receptors, Prostaglandin E, EP2 Subtype</subject><subject>Semen - physiology</subject><subject>Signal Transduction</subject><subject>Transcriptional Activation - physiology</subject><subject>Up-Regulation</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhQMC0WFArNgiCwnEJtSPxHE2SKgaHlIlFsA68tg3My6JHWxn2v577jBDS9mwsiV_Puce-xTFc0bfMtqK0-08RphOLQyCq_vFglWSllzU9EGxoFyqkjHJTorHKV1QilslHxUnTLa0bmS9uPfsK4zO64FMg06jJtpbMsWQst4MuHeerDiZpzLCZh50BtK7dQxrhDPZxHCZt6TXJodIOIGrKUJKLniC98DbMEKODsW1BR-Mjsb5gCYGhiGRndNkVSaIDtLR0wdnS04iGJhQsxzBOjS1JEftE_q4nc57_dCTvAUCk7MQR3S4O8sfgd9x4Apv7y0xQCTJbTDuTR5LfmD8BGTSeXupr58UD3s9JHh6XJfF9w-rb2efyvMvHz-fvT8vTVXvH7UVVBvLW6msbfq2l81aMCqqtdKG93WtWN1YoQTXyggrQEAvDFWNsbRiqhLL4t1Bd5rXmNKAxyGHbopu1PG6C9p1d0-823absOu4bKu2FSjw-igQw88ZUu5Gl_YptYcwp04qIZsGG7IsXv4DXoQ54hukjjPM0fJaIVQeIIP_kCL0N5Mw2u171h161h16hvyLv8e_pY_FQuDVEdDJ6KHH_zMu3XIKTaVqkHtz4MI8_cfzF8BW9Fc</recordid><startdate>2007</startdate><enddate>2007</enddate><creator>Battersby, S.</creator><creator>Sales, K.J.</creator><creator>Williams, A.R.</creator><creator>Anderson, R.A.</creator><creator>Gardner, S.</creator><creator>Jabbour, H.N.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>2007</creationdate><title>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</title><author>Battersby, S. ; Sales, K.J. ; Williams, A.R. ; Anderson, R.A. ; Gardner, S. ; Jabbour, H.N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cyclic AMP - metabolism</topic><topic>Dinoprostone - physiology</topic><topic>Endometrial Neoplasms - metabolism</topic><topic>ErbB Receptors - physiology</topic><topic>Extracellular Signal-Regulated MAP Kinases - physiology</topic><topic>Female</topic><topic>Fibroblast Growth Factor 2 - biosynthesis</topic><topic>Gene Expression Regulation</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Fluorescence</topic><topic>Phosphorylation - drug effects</topic><topic>Proto-Oncogene Proteins pp60(c-src) - metabolism</topic><topic>Receptors, Prostaglandin E - physiology</topic><topic>Receptors, Prostaglandin E, EP2 Subtype</topic><topic>Semen - physiology</topic><topic>Signal Transduction</topic><topic>Transcriptional Activation - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Battersby, S.</creatorcontrib><creatorcontrib>Sales, K.J.</creatorcontrib><creatorcontrib>Williams, A.R.</creatorcontrib><creatorcontrib>Anderson, R.A.</creatorcontrib><creatorcontrib>Gardner, S.</creatorcontrib><creatorcontrib>Jabbour, H.N.</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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Battersby, S.</au><au>Sales, K.J.</au><au>Williams, A.R.</au><au>Anderson, R.A.</au><au>Gardner, S.</au><au>Jabbour, H.N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</atitle><jtitle>Human reproduction (Oxford)</jtitle><stitle>Hum Reprod</stitle><addtitle>Hum Reprod</addtitle><date>2007</date><risdate>2007</risdate><volume>22</volume><issue>1</issue><spage>36</spage><epage>44</epage><pages>36-44</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><coden>HUREEE</coden><abstract>Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>16905765</pmid><doi>10.1093/humrep/del328</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenocarcinoma - metabolism Biological and medical sciences Cell Line, Tumor Cyclic AMP - metabolism Dinoprostone - physiology Endometrial Neoplasms - metabolism ErbB Receptors - physiology Extracellular Signal-Regulated MAP Kinases - physiology Female Fibroblast Growth Factor 2 - biosynthesis Gene Expression Regulation Gynecology. Andrology. Obstetrics Humans Male Medical sciences Microscopy, Confocal Microscopy, Fluorescence Phosphorylation - drug effects Proto-Oncogene Proteins pp60(c-src) - metabolism Receptors, Prostaglandin E - physiology Receptors, Prostaglandin E, EP2 Subtype Semen - physiology Signal Transduction Transcriptional Activation - physiology Up-Regulation |
title | Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway |
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