Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells
Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogen...
Gespeichert in:
Veröffentlicht in: | BMC genomics 2015-05, Vol.16 (1), p.367-367, Article 367 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 367 |
---|---|
container_issue | 1 |
container_start_page | 367 |
container_title | BMC genomics |
container_volume | 16 |
creator | Dago, Dougba Noel Scafoglio, Claudio Rinaldi, Antonio Memoli, Domenico Giurato, Giorgio Nassa, Giovanni Ravo, Maria Rizzo, Francesca Tarallo, Roberta Weisz, Alessandro |
description | Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERβ in cancer cells. We have previously described the ERβ and ERα interactomes from BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERα and ERβ pathways. Guided by these findings, here we performed RNA sequencing to investigate in depth the differences in the early transcriptional events and RNA splicing patterns induced by estradiol in cells expressing ERα alone or ERα and ERβ.
Exon skipping was the most abundant splicing event in the post-transcriptional regulation by estradiol. We identified several splicing events induced by ERα alone and by ERα+ERβ, demonstrating for the first time that ERβ significantly affects estrogen-induced splicing in BC cells, as revealed by modification of a subset of ERα-dependent splicing by ERβ, as well as by the presence of splicing isoforms only in ERβ+cells. In particular, we observed that ERβ+BC cell lines exhibited around 2-fold more splicing events than the ERβ- cells. Interestingly, we identified putative direct targets of ERβ-mediated alternative splicing by correlating the genomic locations of ERβ and ERα binding sites with estradiol-induced differential splicing in the corresponding genes.
Taken together, these results demonstrate that ERβ significantly affects estrogen-induced early transcription and mRNA splicing in hormone-responsive BC cells, providing novel information on the biological role of ERβ in these tumors. |
doi_str_mv | 10.1186/s12864-015-1541-1 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4424892</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A541364715</galeid><sourcerecordid>A541364715</sourcerecordid><originalsourceid>FETCH-LOGICAL-c570t-62f3387bfa88c11804066cde33a11a1982b86fc25de8eafc8cd8b042e1b165173</originalsourceid><addsrcrecordid>eNptktFr1TAYxYs43Jz-Ab5IwJf50C1f2qTpi3AZ0w3GBlOfQ5p-7SJtUpN06H9vLncbuyB5SEh-58D5coriA9BTACnOIjAp6pICL4HXUMKr4gjqBkoGon794nxYvI3xF6XQSMbfFIeMt1y0II4KdRFT8CM6EtDgknwgHSZN7LxokyK592H2Dkvr-tVgT_SUMDid7AOS-e5mQ-IyWWPdSKwjXUAdEzHaGQzE4DTFd8XBoKeI7x_34-Ln14sf55fl9e23q_PNdWl4Q1Mp2FBVsukGLaXJ2WhNhTA9VpUG0NBK1kkxGMZ7lKgHI00vO1ozhA4Eh6Y6Lr7sfJe1m7E36FLQk1qCnXX4q7y2av_F2Xs1-gdV16yWLcsGJ48Gwf9eMSY127iNoB36NSoQkjKgbUUz-mmHjnpCZd3gs6PZ4mqTv6ESeew8U6f_ofLqcbYmz3Sw-X5P8HlPkJmEf9Ko1xjV1fe7fRZ2rAk-xoDDc1KgatsNteuGyt1Q224oyJqPL0f0rHgqQ_UPDQm0Nw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1680210930</pqid></control><display><type>article</type><title>Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerNature Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>PubMed Central</source><creator>Dago, Dougba Noel ; Scafoglio, Claudio ; Rinaldi, Antonio ; Memoli, Domenico ; Giurato, Giorgio ; Nassa, Giovanni ; Ravo, Maria ; Rizzo, Francesca ; Tarallo, Roberta ; Weisz, Alessandro</creator><creatorcontrib>Dago, Dougba Noel ; Scafoglio, Claudio ; Rinaldi, Antonio ; Memoli, Domenico ; Giurato, Giorgio ; Nassa, Giovanni ; Ravo, Maria ; Rizzo, Francesca ; Tarallo, Roberta ; Weisz, Alessandro</creatorcontrib><description>Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERβ in cancer cells. We have previously described the ERβ and ERα interactomes from BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERα and ERβ pathways. Guided by these findings, here we performed RNA sequencing to investigate in depth the differences in the early transcriptional events and RNA splicing patterns induced by estradiol in cells expressing ERα alone or ERα and ERβ.
Exon skipping was the most abundant splicing event in the post-transcriptional regulation by estradiol. We identified several splicing events induced by ERα alone and by ERα+ERβ, demonstrating for the first time that ERβ significantly affects estrogen-induced splicing in BC cells, as revealed by modification of a subset of ERα-dependent splicing by ERβ, as well as by the presence of splicing isoforms only in ERβ+cells. In particular, we observed that ERβ+BC cell lines exhibited around 2-fold more splicing events than the ERβ- cells. Interestingly, we identified putative direct targets of ERβ-mediated alternative splicing by correlating the genomic locations of ERβ and ERα binding sites with estradiol-induced differential splicing in the corresponding genes.
Taken together, these results demonstrate that ERβ significantly affects estrogen-induced early transcription and mRNA splicing in hormone-responsive BC cells, providing novel information on the biological role of ERβ in these tumors.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/s12864-015-1541-1</identifier><identifier>PMID: 25956916</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Alternative Splicing - drug effects ; Analysis ; Breast Neoplasms - pathology ; Estradiol ; Estradiol - pharmacology ; Estrogen Receptor alpha - metabolism ; Estrogen Receptor beta - deficiency ; Estrogen Receptor beta - metabolism ; Estrogens - pharmacology ; Genetic transcription ; High-Throughput Nucleotide Sequencing ; Humans ; MCF-7 Cells ; Physiological aspects ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - genetics ; RNA sequencing ; RNA, Messenger - genetics ; Sequence Analysis, RNA</subject><ispartof>BMC genomics, 2015-05, Vol.16 (1), p.367-367, Article 367</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Dago et al.; licensee BioMed Central. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-62f3387bfa88c11804066cde33a11a1982b86fc25de8eafc8cd8b042e1b165173</citedby><cites>FETCH-LOGICAL-c570t-62f3387bfa88c11804066cde33a11a1982b86fc25de8eafc8cd8b042e1b165173</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/PMC4424892/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424892/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25956916$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dago, Dougba Noel</creatorcontrib><creatorcontrib>Scafoglio, Claudio</creatorcontrib><creatorcontrib>Rinaldi, Antonio</creatorcontrib><creatorcontrib>Memoli, Domenico</creatorcontrib><creatorcontrib>Giurato, Giorgio</creatorcontrib><creatorcontrib>Nassa, Giovanni</creatorcontrib><creatorcontrib>Ravo, Maria</creatorcontrib><creatorcontrib>Rizzo, Francesca</creatorcontrib><creatorcontrib>Tarallo, Roberta</creatorcontrib><creatorcontrib>Weisz, Alessandro</creatorcontrib><title>Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells</title><title>BMC genomics</title><addtitle>BMC Genomics</addtitle><description>Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERβ in cancer cells. We have previously described the ERβ and ERα interactomes from BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERα and ERβ pathways. Guided by these findings, here we performed RNA sequencing to investigate in depth the differences in the early transcriptional events and RNA splicing patterns induced by estradiol in cells expressing ERα alone or ERα and ERβ.
Exon skipping was the most abundant splicing event in the post-transcriptional regulation by estradiol. We identified several splicing events induced by ERα alone and by ERα+ERβ, demonstrating for the first time that ERβ significantly affects estrogen-induced splicing in BC cells, as revealed by modification of a subset of ERα-dependent splicing by ERβ, as well as by the presence of splicing isoforms only in ERβ+cells. In particular, we observed that ERβ+BC cell lines exhibited around 2-fold more splicing events than the ERβ- cells. Interestingly, we identified putative direct targets of ERβ-mediated alternative splicing by correlating the genomic locations of ERβ and ERα binding sites with estradiol-induced differential splicing in the corresponding genes.
Taken together, these results demonstrate that ERβ significantly affects estrogen-induced early transcription and mRNA splicing in hormone-responsive BC cells, providing novel information on the biological role of ERβ in these tumors.</description><subject>Alternative Splicing - drug effects</subject><subject>Analysis</subject><subject>Breast Neoplasms - pathology</subject><subject>Estradiol</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen Receptor beta - deficiency</subject><subject>Estrogen Receptor beta - metabolism</subject><subject>Estrogens - pharmacology</subject><subject>Genetic transcription</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>MCF-7 Cells</subject><subject>Physiological aspects</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>RNA sequencing</subject><subject>RNA, Messenger - genetics</subject><subject>Sequence Analysis, RNA</subject><issn>1471-2164</issn><issn>1471-2164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptktFr1TAYxYs43Jz-Ab5IwJf50C1f2qTpi3AZ0w3GBlOfQ5p-7SJtUpN06H9vLncbuyB5SEh-58D5coriA9BTACnOIjAp6pICL4HXUMKr4gjqBkoGon794nxYvI3xF6XQSMbfFIeMt1y0II4KdRFT8CM6EtDgknwgHSZN7LxokyK592H2Dkvr-tVgT_SUMDid7AOS-e5mQ-IyWWPdSKwjXUAdEzHaGQzE4DTFd8XBoKeI7x_34-Ln14sf55fl9e23q_PNdWl4Q1Mp2FBVsukGLaXJ2WhNhTA9VpUG0NBK1kkxGMZ7lKgHI00vO1ozhA4Eh6Y6Lr7sfJe1m7E36FLQk1qCnXX4q7y2av_F2Xs1-gdV16yWLcsGJ48Gwf9eMSY127iNoB36NSoQkjKgbUUz-mmHjnpCZd3gs6PZ4mqTv6ESeew8U6f_ofLqcbYmz3Sw-X5P8HlPkJmEf9Ko1xjV1fe7fRZ2rAk-xoDDc1KgatsNteuGyt1Q224oyJqPL0f0rHgqQ_UPDQm0Nw</recordid><startdate>20150509</startdate><enddate>20150509</enddate><creator>Dago, Dougba Noel</creator><creator>Scafoglio, Claudio</creator><creator>Rinaldi, Antonio</creator><creator>Memoli, Domenico</creator><creator>Giurato, Giorgio</creator><creator>Nassa, Giovanni</creator><creator>Ravo, Maria</creator><creator>Rizzo, Francesca</creator><creator>Tarallo, Roberta</creator><creator>Weisz, Alessandro</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150509</creationdate><title>Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells</title><author>Dago, Dougba Noel ; Scafoglio, Claudio ; Rinaldi, Antonio ; Memoli, Domenico ; Giurato, Giorgio ; Nassa, Giovanni ; Ravo, Maria ; Rizzo, Francesca ; Tarallo, Roberta ; Weisz, Alessandro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-62f3387bfa88c11804066cde33a11a1982b86fc25de8eafc8cd8b042e1b165173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alternative Splicing - drug effects</topic><topic>Analysis</topic><topic>Breast Neoplasms - pathology</topic><topic>Estradiol</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogen Receptor beta - deficiency</topic><topic>Estrogen Receptor beta - metabolism</topic><topic>Estrogens - pharmacology</topic><topic>Genetic transcription</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>MCF-7 Cells</topic><topic>Physiological aspects</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>RNA sequencing</topic><topic>RNA, Messenger - genetics</topic><topic>Sequence Analysis, RNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dago, Dougba Noel</creatorcontrib><creatorcontrib>Scafoglio, Claudio</creatorcontrib><creatorcontrib>Rinaldi, Antonio</creatorcontrib><creatorcontrib>Memoli, Domenico</creatorcontrib><creatorcontrib>Giurato, Giorgio</creatorcontrib><creatorcontrib>Nassa, Giovanni</creatorcontrib><creatorcontrib>Ravo, Maria</creatorcontrib><creatorcontrib>Rizzo, Francesca</creatorcontrib><creatorcontrib>Tarallo, Roberta</creatorcontrib><creatorcontrib>Weisz, Alessandro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dago, Dougba Noel</au><au>Scafoglio, Claudio</au><au>Rinaldi, Antonio</au><au>Memoli, Domenico</au><au>Giurato, Giorgio</au><au>Nassa, Giovanni</au><au>Ravo, Maria</au><au>Rizzo, Francesca</au><au>Tarallo, Roberta</au><au>Weisz, Alessandro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells</atitle><jtitle>BMC genomics</jtitle><addtitle>BMC Genomics</addtitle><date>2015-05-09</date><risdate>2015</risdate><volume>16</volume><issue>1</issue><spage>367</spage><epage>367</epage><pages>367-367</pages><artnum>367</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERβ in cancer cells. We have previously described the ERβ and ERα interactomes from BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERα and ERβ pathways. Guided by these findings, here we performed RNA sequencing to investigate in depth the differences in the early transcriptional events and RNA splicing patterns induced by estradiol in cells expressing ERα alone or ERα and ERβ.
Exon skipping was the most abundant splicing event in the post-transcriptional regulation by estradiol. We identified several splicing events induced by ERα alone and by ERα+ERβ, demonstrating for the first time that ERβ significantly affects estrogen-induced splicing in BC cells, as revealed by modification of a subset of ERα-dependent splicing by ERβ, as well as by the presence of splicing isoforms only in ERβ+cells. In particular, we observed that ERβ+BC cell lines exhibited around 2-fold more splicing events than the ERβ- cells. Interestingly, we identified putative direct targets of ERβ-mediated alternative splicing by correlating the genomic locations of ERβ and ERα binding sites with estradiol-induced differential splicing in the corresponding genes.
Taken together, these results demonstrate that ERβ significantly affects estrogen-induced early transcription and mRNA splicing in hormone-responsive BC cells, providing novel information on the biological role of ERβ in these tumors.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25956916</pmid><doi>10.1186/s12864-015-1541-1</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1471-2164 |
ispartof | BMC genomics, 2015-05, Vol.16 (1), p.367-367, Article 367 |
issn | 1471-2164 1471-2164 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4424892 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerNature Journals; PubMed Central Open Access; Springer Nature OA Free Journals; PubMed Central |
subjects | Alternative Splicing - drug effects Analysis Breast Neoplasms - pathology Estradiol Estradiol - pharmacology Estrogen Receptor alpha - metabolism Estrogen Receptor beta - deficiency Estrogen Receptor beta - metabolism Estrogens - pharmacology Genetic transcription High-Throughput Nucleotide Sequencing Humans MCF-7 Cells Physiological aspects Promoter Regions, Genetic - drug effects Promoter Regions, Genetic - genetics RNA sequencing RNA, Messenger - genetics Sequence Analysis, RNA |
title | Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T04%3A23%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Estrogen%20receptor%20beta%20impacts%20hormone-induced%20alternative%20mRNA%20splicing%20in%20breast%20cancer%20cells&rft.jtitle=BMC%20genomics&rft.au=Dago,%20Dougba%20Noel&rft.date=2015-05-09&rft.volume=16&rft.issue=1&rft.spage=367&rft.epage=367&rft.pages=367-367&rft.artnum=367&rft.issn=1471-2164&rft.eissn=1471-2164&rft_id=info:doi/10.1186/s12864-015-1541-1&rft_dat=%3Cgale_pubme%3EA541364715%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1680210930&rft_id=info:pmid/25956916&rft_galeid=A541364715&rfr_iscdi=true |