The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5
Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induce...
Gespeichert in:
| Veröffentlicht in: | Molecular endocrinology (Baltimore, Md.) Md.), 2010-07, Vol.24 (7), p.1380-1392 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1392 |
|---|---|
| container_issue | 7 |
| container_start_page | 1380 |
| container_title | Molecular endocrinology (Baltimore, Md.) |
| container_volume | 24 |
| creator | Hilton, H. N Kalyuga, M Cowley, M. J Alles, M. C Lee, H. J Caldon, C. E Blazek, K Kaplan, W Musgrove, E. A Daly, R. J Naylor, M. J Graham, J. D Clarke, C. L Ormandy, C. J |
| description | Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
In T47D breast cancer cells direct progestin induction of the ETS transcription factor Elf5 tempers antiproliferative progestin action via regulation of cell cycle control genes. |
| doi_str_mv | 10.1210/me.2009-0516 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5417466</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1210/me.2009-0516</oup_id><sourcerecordid>733477489</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-20845c1fc24aa1325615b68dab5b6747d2ee91a6fbbe605bdbb92ca47f417b5a3</originalsourceid><addsrcrecordid>eNp1kUFv1DAQhS1ERZfCjTPyjQtp7cRO4gvSsmyhUiWQCGfLdsatq8QOdlKp_4KfjJddWpDa0xzm-Xvj9xB6Q8kpLSk5G-G0JEQUhNP6GVpRwVghBG2eoxVp27ZoWyKO0cuUbgihjLf0BTous1hUFV2hX9014LWf3RTD4CxENbtbwFtrwcwJB4u_xXAFaXY-Yedxx5pP-GMElWa8Ud5AxBsYhoTXEXAH4wQReqzvHp7hC98vZnbB72hzttt233EXlU8muunP4lyZOUS8HSx_hY6sGhK8PswT9ON8222-FJdfP19s1peFYVzMRUlaxg21pmRK0arkNeW6bnul82hY05cAgqraag014brXWpRGscYy2miuqhP0Yc-dFj1Cb8DPUQ1yim5U8U4G5eT_G--u5VW4lTwDWF1nwLsDIIafS_6qHF0yOQvlISxJNlXFmoa1Iivf75UmhpQi2HsXSuSuQzmC3HUodx1m-dt_L7sX_y3twTks01Oo4oCq9krwfchpe5gipCRvwhJ9TvfxA34DR3G24w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733477489</pqid></control><display><type>article</type><title>The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Hilton, H. N ; Kalyuga, M ; Cowley, M. J ; Alles, M. C ; Lee, H. J ; Caldon, C. E ; Blazek, K ; Kaplan, W ; Musgrove, E. A ; Daly, R. J ; Naylor, M. J ; Graham, J. D ; Clarke, C. L ; Ormandy, C. J</creator><creatorcontrib>Hilton, H. N ; Kalyuga, M ; Cowley, M. J ; Alles, M. C ; Lee, H. J ; Caldon, C. E ; Blazek, K ; Kaplan, W ; Musgrove, E. A ; Daly, R. J ; Naylor, M. J ; Graham, J. D ; Clarke, C. L ; Ormandy, C. J</creatorcontrib><description>Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
In T47D breast cancer cells direct progestin induction of the ETS transcription factor Elf5 tempers antiproliferative progestin action via regulation of cell cycle control genes.</description><identifier>ISSN: 0888-8809</identifier><identifier>EISSN: 1944-9917</identifier><identifier>DOI: 10.1210/me.2009-0516</identifier><identifier>PMID: 20519331</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Female ; Humans ; Mifepristone - pharmacology ; Oligonucleotide Array Sequence Analysis ; Original Research ; Progestins - pharmacology ; Progestins - therapeutic use ; Proto-Oncogene Proteins c-ets - metabolism ; RNA Interference</subject><ispartof>Molecular endocrinology (Baltimore, Md.), 2010-07, Vol.24 (7), p.1380-1392</ispartof><rights>Copyright © 2010 by The Endocrine Society 2010</rights><rights>2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-20845c1fc24aa1325615b68dab5b6747d2ee91a6fbbe605bdbb92ca47f417b5a3</citedby><cites>FETCH-LOGICAL-c459t-20845c1fc24aa1325615b68dab5b6747d2ee91a6fbbe605bdbb92ca47f417b5a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20519331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hilton, H. N</creatorcontrib><creatorcontrib>Kalyuga, M</creatorcontrib><creatorcontrib>Cowley, M. J</creatorcontrib><creatorcontrib>Alles, M. C</creatorcontrib><creatorcontrib>Lee, H. J</creatorcontrib><creatorcontrib>Caldon, C. E</creatorcontrib><creatorcontrib>Blazek, K</creatorcontrib><creatorcontrib>Kaplan, W</creatorcontrib><creatorcontrib>Musgrove, E. A</creatorcontrib><creatorcontrib>Daly, R. J</creatorcontrib><creatorcontrib>Naylor, M. J</creatorcontrib><creatorcontrib>Graham, J. D</creatorcontrib><creatorcontrib>Clarke, C. L</creatorcontrib><creatorcontrib>Ormandy, C. J</creatorcontrib><title>The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5</title><title>Molecular endocrinology (Baltimore, Md.)</title><addtitle>Mol Endocrinol</addtitle><description>Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
In T47D breast cancer cells direct progestin induction of the ETS transcription factor Elf5 tempers antiproliferative progestin action via regulation of cell cycle control genes.</description><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>Mifepristone - pharmacology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Original Research</subject><subject>Progestins - pharmacology</subject><subject>Progestins - therapeutic use</subject><subject>Proto-Oncogene Proteins c-ets - metabolism</subject><subject>RNA Interference</subject><issn>0888-8809</issn><issn>1944-9917</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFv1DAQhS1ERZfCjTPyjQtp7cRO4gvSsmyhUiWQCGfLdsatq8QOdlKp_4KfjJddWpDa0xzm-Xvj9xB6Q8kpLSk5G-G0JEQUhNP6GVpRwVghBG2eoxVp27ZoWyKO0cuUbgihjLf0BTous1hUFV2hX9014LWf3RTD4CxENbtbwFtrwcwJB4u_xXAFaXY-Yedxx5pP-GMElWa8Ud5AxBsYhoTXEXAH4wQReqzvHp7hC98vZnbB72hzttt233EXlU8muunP4lyZOUS8HSx_hY6sGhK8PswT9ON8222-FJdfP19s1peFYVzMRUlaxg21pmRK0arkNeW6bnul82hY05cAgqraag014brXWpRGscYy2miuqhP0Yc-dFj1Cb8DPUQ1yim5U8U4G5eT_G--u5VW4lTwDWF1nwLsDIIafS_6qHF0yOQvlISxJNlXFmoa1Iivf75UmhpQi2HsXSuSuQzmC3HUodx1m-dt_L7sX_y3twTks01Oo4oCq9krwfchpe5gipCRvwhJ9TvfxA34DR3G24w</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Hilton, H. N</creator><creator>Kalyuga, M</creator><creator>Cowley, M. J</creator><creator>Alles, M. C</creator><creator>Lee, H. J</creator><creator>Caldon, C. E</creator><creator>Blazek, K</creator><creator>Kaplan, W</creator><creator>Musgrove, E. A</creator><creator>Daly, R. J</creator><creator>Naylor, M. J</creator><creator>Graham, J. D</creator><creator>Clarke, C. L</creator><creator>Ormandy, C. J</creator><general>Endocrine Society</general><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100701</creationdate><title>The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5</title><author>Hilton, H. N ; Kalyuga, M ; Cowley, M. J ; Alles, M. C ; Lee, H. J ; Caldon, C. E ; Blazek, K ; Kaplan, W ; Musgrove, E. A ; Daly, R. J ; Naylor, M. J ; Graham, J. D ; Clarke, C. L ; Ormandy, C. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-20845c1fc24aa1325615b68dab5b6747d2ee91a6fbbe605bdbb92ca47f417b5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Female</topic><topic>Humans</topic><topic>Mifepristone - pharmacology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Original Research</topic><topic>Progestins - pharmacology</topic><topic>Progestins - therapeutic use</topic><topic>Proto-Oncogene Proteins c-ets - metabolism</topic><topic>RNA Interference</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hilton, H. N</creatorcontrib><creatorcontrib>Kalyuga, M</creatorcontrib><creatorcontrib>Cowley, M. J</creatorcontrib><creatorcontrib>Alles, M. C</creatorcontrib><creatorcontrib>Lee, H. J</creatorcontrib><creatorcontrib>Caldon, C. E</creatorcontrib><creatorcontrib>Blazek, K</creatorcontrib><creatorcontrib>Kaplan, W</creatorcontrib><creatorcontrib>Musgrove, E. A</creatorcontrib><creatorcontrib>Daly, R. J</creatorcontrib><creatorcontrib>Naylor, M. J</creatorcontrib><creatorcontrib>Graham, J. D</creatorcontrib><creatorcontrib>Clarke, C. L</creatorcontrib><creatorcontrib>Ormandy, C. J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hilton, H. N</au><au>Kalyuga, M</au><au>Cowley, M. J</au><au>Alles, M. C</au><au>Lee, H. J</au><au>Caldon, C. E</au><au>Blazek, K</au><au>Kaplan, W</au><au>Musgrove, E. A</au><au>Daly, R. J</au><au>Naylor, M. J</au><au>Graham, J. D</au><au>Clarke, C. L</au><au>Ormandy, C. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5</atitle><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle><addtitle>Mol Endocrinol</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>24</volume><issue>7</issue><spage>1380</spage><epage>1392</epage><pages>1380-1392</pages><issn>0888-8809</issn><eissn>1944-9917</eissn><abstract>Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
In T47D breast cancer cells direct progestin induction of the ETS transcription factor Elf5 tempers antiproliferative progestin action via regulation of cell cycle control genes.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>20519331</pmid><doi>10.1210/me.2009-0516</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0888-8809 |
| ispartof | Molecular endocrinology (Baltimore, Md.), 2010-07, Vol.24 (7), p.1380-1392 |
| issn | 0888-8809 1944-9917 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5417466 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Cell Line, Tumor Cell Proliferation - drug effects Female Humans Mifepristone - pharmacology Oligonucleotide Array Sequence Analysis Original Research Progestins - pharmacology Progestins - therapeutic use Proto-Oncogene Proteins c-ets - metabolism RNA Interference |
| title | The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T07%3A19%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Antiproliferative%20Effects%20of%20Progestins%20in%20T47D%20Breast%20Cancer%20Cells%20Are%20Tempered%20by%20Progestin%20Induction%20of%20the%20ETS%20Transcription%20Factor%20Elf5&rft.jtitle=Molecular%20endocrinology%20(Baltimore,%20Md.)&rft.au=Hilton,%20H.%20N&rft.date=2010-07-01&rft.volume=24&rft.issue=7&rft.spage=1380&rft.epage=1392&rft.pages=1380-1392&rft.issn=0888-8809&rft.eissn=1944-9917&rft_id=info:doi/10.1210/me.2009-0516&rft_dat=%3Cproquest_pubme%3E733477489%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733477489&rft_id=info:pmid/20519331&rft_oup_id=10.1210/me.2009-0516&rfr_iscdi=true |