Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol
► ERΔ3 transgenic mice express the mouse ERα variant lacking the second zinc finger. ► Many tissues express ERΔ3; a higher ratio of ERα to ERΔ3 occurs in the uterus. ► Neonatal diethylstilbestrol accelerated uterine cancer in ERΔ3 versus wild-type mice. ► Estrogen-responsive genes (Pgr, Ltf) are not...
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| Veröffentlicht in: | Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2012-12, Vol.34 (4), p.512-521 |
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| creator | Davis, Vicki L. Newbold, Retha R. Couse, John F. Rea, Sheri L. Gallagher, Katie M. Hamilton, Katherine J. Goulding, Eugenia H. Jefferson, Wendy Eddy, E.M. Bullock, Bill C. Korach, Kenneth S. |
| description | ► ERΔ3 transgenic mice express the mouse ERα variant lacking the second zinc finger. ► Many tissues express ERΔ3; a higher ratio of ERα to ERΔ3 occurs in the uterus. ► Neonatal diethylstilbestrol accelerated uterine cancer in ERΔ3 versus wild-type mice. ► Estrogen-responsive genes (Pgr, Ltf) are not modified by ERΔ3 in the uterus. ► 17β-Estradiol serum levels are higher in ERΔ3 than wild-type mice.
ERΔ3 transgenic mice expressing a dominant negative estrogen receptor α (ERα) variant lacking the second zinc finger in the DNA binding domain were developed to examine its potential to inhibit estrogen action in vivo. To investigate if ERΔ3 expression influences uterine carcinogenesis, ERΔ3 transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1–5. Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old ERΔ3 mice compared to 49% of wild-type females (p |
| doi_str_mv | 10.1016/j.reprotox.2012.08.005 |
| format | Article |
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ERΔ3 transgenic mice expressing a dominant negative estrogen receptor α (ERα) variant lacking the second zinc finger in the DNA binding domain were developed to examine its potential to inhibit estrogen action in vivo. To investigate if ERΔ3 expression influences uterine carcinogenesis, ERΔ3 transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1–5. Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old ERΔ3 mice compared to 49% of wild-type females (p<0.016). ERΔ3 did not inhibit the expression of the estrogen-responsive progesterone receptor and lactoferrin genes in the presence of ERα or modify their expression in ERα knockout (αERKO) mice. Higher circulating 17β-estradiol levels and non-classical signaling by ERΔ3 may be related to the earlier incidence of uterine cancer. These findings indicate that expression of this ERα variant can influence determining events in uterine cancer development and its natural occurrence in the human uterus would unlikely be protective.</description><identifier>ISSN: 0890-6238</identifier><identifier>EISSN: 1873-1708</identifier><identifier>DOI: 10.1016/j.reprotox.2012.08.005</identifier><identifier>PMID: 22989549</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Biological and medical sciences ; Carcinogens - toxicity ; Diethylstilbestrol ; Diethylstilbestrol - toxicity ; Dominant negative receptor ; Embryology: invertebrates and vertebrates. Teratology ; ERα variants ; ERΔ3 ; Estradiol - blood ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Estrogens - toxicity ; Female ; Female genital diseases ; Fundamental and applied biological sciences. Psychology ; Gynecology. Andrology. Obstetrics ; Lactoferrin ; Male ; Medical sciences ; Mice ; Mice, Transgenic ; Non-classical ER signaling ; Progesterone - blood ; Progesterone receptor ; Teratology. Teratogens ; Tumors ; Uterine cancer ; Uterine Neoplasms - chemically induced ; Uterine Neoplasms - genetics ; Uterine Neoplasms - metabolism</subject><ispartof>Reproductive toxicology (Elmsford, N.Y.), 2012-12, Vol.34 (4), p.512-521</ispartof><rights>2012</rights><rights>2014 INIST-CNRS</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-2e95197f4c26c48e61596a28383ce2627c951de29df5014cacc275a3249c3d633</citedby><cites>FETCH-LOGICAL-c567t-2e95197f4c26c48e61596a28383ce2627c951de29df5014cacc275a3249c3d633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.reprotox.2012.08.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26777649$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22989549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Davis, Vicki L.</creatorcontrib><creatorcontrib>Newbold, Retha R.</creatorcontrib><creatorcontrib>Couse, John F.</creatorcontrib><creatorcontrib>Rea, Sheri L.</creatorcontrib><creatorcontrib>Gallagher, Katie M.</creatorcontrib><creatorcontrib>Hamilton, Katherine J.</creatorcontrib><creatorcontrib>Goulding, Eugenia H.</creatorcontrib><creatorcontrib>Jefferson, Wendy</creatorcontrib><creatorcontrib>Eddy, E.M.</creatorcontrib><creatorcontrib>Bullock, Bill C.</creatorcontrib><creatorcontrib>Korach, Kenneth S.</creatorcontrib><title>Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol</title><title>Reproductive toxicology (Elmsford, N.Y.)</title><addtitle>Reprod Toxicol</addtitle><description>► ERΔ3 transgenic mice express the mouse ERα variant lacking the second zinc finger. ► Many tissues express ERΔ3; a higher ratio of ERα to ERΔ3 occurs in the uterus. ► Neonatal diethylstilbestrol accelerated uterine cancer in ERΔ3 versus wild-type mice. ► Estrogen-responsive genes (Pgr, Ltf) are not modified by ERΔ3 in the uterus. ► 17β-Estradiol serum levels are higher in ERΔ3 than wild-type mice.
ERΔ3 transgenic mice expressing a dominant negative estrogen receptor α (ERα) variant lacking the second zinc finger in the DNA binding domain were developed to examine its potential to inhibit estrogen action in vivo. To investigate if ERΔ3 expression influences uterine carcinogenesis, ERΔ3 transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1–5. Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old ERΔ3 mice compared to 49% of wild-type females (p<0.016). ERΔ3 did not inhibit the expression of the estrogen-responsive progesterone receptor and lactoferrin genes in the presence of ERα or modify their expression in ERα knockout (αERKO) mice. Higher circulating 17β-estradiol levels and non-classical signaling by ERΔ3 may be related to the earlier incidence of uterine cancer. These findings indicate that expression of this ERα variant can influence determining events in uterine cancer development and its natural occurrence in the human uterus would unlikely be protective.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biological and medical sciences</subject><subject>Carcinogens - toxicity</subject><subject>Diethylstilbestrol</subject><subject>Diethylstilbestrol - toxicity</subject><subject>Dominant negative receptor</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>ERα variants</subject><subject>ERΔ3</subject><subject>Estradiol - blood</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogens - toxicity</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Lactoferrin</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Non-classical ER signaling</subject><subject>Progesterone - blood</subject><subject>Progesterone receptor</subject><subject>Teratology. Teratogens</subject><subject>Tumors</subject><subject>Uterine cancer</subject><subject>Uterine Neoplasms - chemically induced</subject><subject>Uterine Neoplasms - genetics</subject><subject>Uterine Neoplasms - metabolism</subject><issn>0890-6238</issn><issn>1873-1708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEUhS0EomnhFSpvWM7U9sz4Z4NAVfmRKrGBteXYdxJHE3tkO1HzOH1TnKYNsGJlyfc7516dg9A1JS0llN9s2gRziiU-tIxQ1hLZEjK8QgsqRddQQeRrtCBSkYazTl6gy5w3hJBeKPEWXTCmpBp6tUCPdw9zgpx9DDiO2GAXtz6YUHCAlSl-DxhySXEFASewMJeYsJnmtcF7k_wR9AGXZEKuiLd46y1gYy1MkEyBjHcFkg-ArQkWUqXdzoLDywMua8BzLFA9zjuch7I-TLn4afn0Ob1Db0YzZXj__F6hX1_uft5-a-5_fP1--_m-sQMXpWGgBqrE2FvGbS-B00Fxw2QnOwuMM2Hr3AFTbhwI7W09kYnBdKxXtnO8667Qx5PvvFtuwdl6VjKTnpPfmnTQ0Xj97yT4tV7Fve4p78nQVwN-MrAp5pxgPGsp0cfS9Ea_lKaPpWkidS2tCq__3nyWvbRUgQ_PgMnWTGNN2_r8h-NCCP7EfTpxUHPae0g6Ww81dudrd0W76P93y29p6b_u</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Davis, Vicki L.</creator><creator>Newbold, Retha R.</creator><creator>Couse, John F.</creator><creator>Rea, Sheri L.</creator><creator>Gallagher, Katie M.</creator><creator>Hamilton, Katherine J.</creator><creator>Goulding, Eugenia H.</creator><creator>Jefferson, Wendy</creator><creator>Eddy, E.M.</creator><creator>Bullock, Bill C.</creator><creator>Korach, Kenneth S.</creator><general>Elsevier Inc</general><general>Elsevier</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>5PM</scope></search><sort><creationdate>20121201</creationdate><title>Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol</title><author>Davis, Vicki L. ; Newbold, Retha R. ; Couse, John F. ; Rea, Sheri L. ; Gallagher, Katie M. ; Hamilton, Katherine J. ; Goulding, Eugenia H. ; Jefferson, Wendy ; Eddy, E.M. ; Bullock, Bill C. ; Korach, Kenneth S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-2e95197f4c26c48e61596a28383ce2627c951de29df5014cacc275a3249c3d633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biological and medical sciences</topic><topic>Carcinogens - toxicity</topic><topic>Diethylstilbestrol</topic><topic>Diethylstilbestrol - toxicity</topic><topic>Dominant negative receptor</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>ERα variants</topic><topic>ERΔ3</topic><topic>Estradiol - blood</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogens - toxicity</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Lactoferrin</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Non-classical ER signaling</topic><topic>Progesterone - blood</topic><topic>Progesterone receptor</topic><topic>Teratology. Teratogens</topic><topic>Tumors</topic><topic>Uterine cancer</topic><topic>Uterine Neoplasms - chemically induced</topic><topic>Uterine Neoplasms - genetics</topic><topic>Uterine Neoplasms - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Davis, Vicki L.</creatorcontrib><creatorcontrib>Newbold, Retha R.</creatorcontrib><creatorcontrib>Couse, John F.</creatorcontrib><creatorcontrib>Rea, Sheri L.</creatorcontrib><creatorcontrib>Gallagher, Katie M.</creatorcontrib><creatorcontrib>Hamilton, Katherine J.</creatorcontrib><creatorcontrib>Goulding, Eugenia H.</creatorcontrib><creatorcontrib>Jefferson, Wendy</creatorcontrib><creatorcontrib>Eddy, E.M.</creatorcontrib><creatorcontrib>Bullock, Bill C.</creatorcontrib><creatorcontrib>Korach, Kenneth S.</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>PubMed Central (Full Participant titles)</collection><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Davis, Vicki L.</au><au>Newbold, Retha R.</au><au>Couse, John F.</au><au>Rea, Sheri L.</au><au>Gallagher, Katie M.</au><au>Hamilton, Katherine J.</au><au>Goulding, Eugenia H.</au><au>Jefferson, Wendy</au><au>Eddy, E.M.</au><au>Bullock, Bill C.</au><au>Korach, Kenneth S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol</atitle><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle><addtitle>Reprod Toxicol</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>34</volume><issue>4</issue><spage>512</spage><epage>521</epage><pages>512-521</pages><issn>0890-6238</issn><eissn>1873-1708</eissn><abstract>► ERΔ3 transgenic mice express the mouse ERα variant lacking the second zinc finger. ► Many tissues express ERΔ3; a higher ratio of ERα to ERΔ3 occurs in the uterus. ► Neonatal diethylstilbestrol accelerated uterine cancer in ERΔ3 versus wild-type mice. ► Estrogen-responsive genes (Pgr, Ltf) are not modified by ERΔ3 in the uterus. ► 17β-Estradiol serum levels are higher in ERΔ3 than wild-type mice.
ERΔ3 transgenic mice expressing a dominant negative estrogen receptor α (ERα) variant lacking the second zinc finger in the DNA binding domain were developed to examine its potential to inhibit estrogen action in vivo. To investigate if ERΔ3 expression influences uterine carcinogenesis, ERΔ3 transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1–5. Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old ERΔ3 mice compared to 49% of wild-type females (p<0.016). ERΔ3 did not inhibit the expression of the estrogen-responsive progesterone receptor and lactoferrin genes in the presence of ERα or modify their expression in ERα knockout (αERKO) mice. Higher circulating 17β-estradiol levels and non-classical signaling by ERΔ3 may be related to the earlier incidence of uterine cancer. These findings indicate that expression of this ERα variant can influence determining events in uterine cancer development and its natural occurrence in the human uterus would unlikely be protective.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22989549</pmid><doi>10.1016/j.reprotox.2012.08.005</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Reproductive toxicology (Elmsford, N.Y.), 2012-12, Vol.34 (4), p.512-521 |
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| subjects | Animals Animals, Newborn Biological and medical sciences Carcinogens - toxicity Diethylstilbestrol Diethylstilbestrol - toxicity Dominant negative receptor Embryology: invertebrates and vertebrates. Teratology ERα variants ERΔ3 Estradiol - blood Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Estrogens - toxicity Female Female genital diseases Fundamental and applied biological sciences. Psychology Gynecology. Andrology. Obstetrics Lactoferrin Male Medical sciences Mice Mice, Transgenic Non-classical ER signaling Progesterone - blood Progesterone receptor Teratology. Teratogens Tumors Uterine cancer Uterine Neoplasms - chemically induced Uterine Neoplasms - genetics Uterine Neoplasms - metabolism |
| title | Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol |
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