CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3
Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. C...
Gespeichert in:
| Veröffentlicht in: | Cancers 2022-11, Vol.14 (21), p.5453 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 21 |
| container_start_page | 5453 |
| container_title | Cancers |
| container_volume | 14 |
| creator | Porras, Lucas Gorse, Faustine Thiombane, Ndeye Khady Gaboury, Louis Mader, Sylvie |
| description | Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR− status in ER+ tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower PGR expression, the clinical PR status does not correlate accurately with the expression of ESR1 or of ER target genes, including PGR itself. We identified carbonic anhydrase 12 (CA12) as an estrogen target gene better correlated with ESR1 than PGR, reflecting CA12 regulation by both ERα and the luminal factor and upstream ESR1 regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ER+PR− tumors expressed CAXII at levels similar to those of ER+PR+ tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ER+PR− breast cancer cell lines. The few ER−PR+ tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors. |
| doi_str_mv | 10.3390/cancers14215453 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9657334</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A745272426</galeid><sourcerecordid>A745272426</sourcerecordid><originalsourceid>FETCH-LOGICAL-c395t-eeefd8de207dcc0c69be0351b184e47539d5d2a8618d43c21d999344f2b269ff3</originalsourceid><addsrcrecordid>eNptks9rFTEQxxdRbKk9ew148fLaTSY_NhdhfdT64EmhPsFbyCaT59bdTU12hf73pj-otjg5zJD5zDeZYarqLa1PAHR96uzkMGXKGRVcwIvqkNWKraTU_OU_8UF1nPNVXQyAKqleVwcgQTSNoofVxbr9vtmQTSaWfF1Sins7I_li009MJMREtsvYT3YgHxPaPJPdMsaUySXul6GQnnQ35OyS2MmT83bXwpvqVbBDxuMHf1R9-3S2W39ebS_ON-t2u3KgxbxCxOAbj-WT3rnaSd1hDYJ2tOHIlQDthWe2kbTxHByjXmsNnAfWMalDgKPqw73u9dKN6B1Oc7KDuU79aNONibY3TzNT_8Ps42-jpVAAvAi8fxBI8deCeTZjnx0Og50wLtkwVUak68IW9N0z9CouqQzljuKSKgXsL7W3A5p-CrG8625FTau4YIpxJgt18h-qHI9j7-KEoS_3TwpO7wtcijknDI890trcroF5tgbwB_jUobM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2734617732</pqid></control><display><type>article</type><title>CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Porras, Lucas ; Gorse, Faustine ; Thiombane, Ndeye Khady ; Gaboury, Louis ; Mader, Sylvie</creator><creatorcontrib>Porras, Lucas ; Gorse, Faustine ; Thiombane, Ndeye Khady ; Gaboury, Louis ; Mader, Sylvie</creatorcontrib><description>Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR− status in ER+ tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower PGR expression, the clinical PR status does not correlate accurately with the expression of ESR1 or of ER target genes, including PGR itself. We identified carbonic anhydrase 12 (CA12) as an estrogen target gene better correlated with ESR1 than PGR, reflecting CA12 regulation by both ERα and the luminal factor and upstream ESR1 regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ER+PR− tumors expressed CAXII at levels similar to those of ER+PR+ tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ER+PR− breast cancer cell lines. The few ER−PR+ tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14215453</identifier><identifier>PMID: 36358871</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Biological markers ; Breast cancer ; Breast tumors ; Cancer therapies ; Care and treatment ; Cell growth ; Drug delivery ; Estrogen ; Estrogen receptors ; Estrogens ; GATA-3 protein ; Gene expression ; Genes ; Genetic aspects ; Health aspects ; Medical prognosis ; Progesterone ; Prognosis ; Proteins ; Receptors ; Sex hormones ; Transcription factors ; Transcriptomes ; Tumor cell lines ; Tumorigenesis ; Tumors ; Xenoestrogens</subject><ispartof>Cancers, 2022-11, Vol.14 (21), p.5453</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-eeefd8de207dcc0c69be0351b184e47539d5d2a8618d43c21d999344f2b269ff3</citedby><cites>FETCH-LOGICAL-c395t-eeefd8de207dcc0c69be0351b184e47539d5d2a8618d43c21d999344f2b269ff3</cites><orcidid>0000-0002-7093-8139 ; 0000-0002-6423-627X ; 0000-0001-8859-6192 ; 0000-0001-8392-998X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657334/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657334/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Porras, Lucas</creatorcontrib><creatorcontrib>Gorse, Faustine</creatorcontrib><creatorcontrib>Thiombane, Ndeye Khady</creatorcontrib><creatorcontrib>Gaboury, Louis</creatorcontrib><creatorcontrib>Mader, Sylvie</creatorcontrib><title>CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3</title><title>Cancers</title><description>Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR− status in ER+ tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower PGR expression, the clinical PR status does not correlate accurately with the expression of ESR1 or of ER target genes, including PGR itself. We identified carbonic anhydrase 12 (CA12) as an estrogen target gene better correlated with ESR1 than PGR, reflecting CA12 regulation by both ERα and the luminal factor and upstream ESR1 regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ER+PR− tumors expressed CAXII at levels similar to those of ER+PR+ tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ER+PR− breast cancer cell lines. The few ER−PR+ tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors.</description><subject>Biological markers</subject><subject>Breast cancer</subject><subject>Breast tumors</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell growth</subject><subject>Drug delivery</subject><subject>Estrogen</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>GATA-3 protein</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Medical prognosis</subject><subject>Progesterone</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Sex hormones</subject><subject>Transcription factors</subject><subject>Transcriptomes</subject><subject>Tumor cell lines</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenoestrogens</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptks9rFTEQxxdRbKk9ew148fLaTSY_NhdhfdT64EmhPsFbyCaT59bdTU12hf73pj-otjg5zJD5zDeZYarqLa1PAHR96uzkMGXKGRVcwIvqkNWKraTU_OU_8UF1nPNVXQyAKqleVwcgQTSNoofVxbr9vtmQTSaWfF1Sins7I_li009MJMREtsvYT3YgHxPaPJPdMsaUySXul6GQnnQ35OyS2MmT83bXwpvqVbBDxuMHf1R9-3S2W39ebS_ON-t2u3KgxbxCxOAbj-WT3rnaSd1hDYJ2tOHIlQDthWe2kbTxHByjXmsNnAfWMalDgKPqw73u9dKN6B1Oc7KDuU79aNONibY3TzNT_8Ps42-jpVAAvAi8fxBI8deCeTZjnx0Og50wLtkwVUak68IW9N0z9CouqQzljuKSKgXsL7W3A5p-CrG8625FTau4YIpxJgt18h-qHI9j7-KEoS_3TwpO7wtcijknDI890trcroF5tgbwB_jUobM</recordid><startdate>20221106</startdate><enddate>20221106</enddate><creator>Porras, Lucas</creator><creator>Gorse, Faustine</creator><creator>Thiombane, Ndeye Khady</creator><creator>Gaboury, Louis</creator><creator>Mader, Sylvie</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7093-8139</orcidid><orcidid>https://orcid.org/0000-0002-6423-627X</orcidid><orcidid>https://orcid.org/0000-0001-8859-6192</orcidid><orcidid>https://orcid.org/0000-0001-8392-998X</orcidid></search><sort><creationdate>20221106</creationdate><title>CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3</title><author>Porras, Lucas ; Gorse, Faustine ; Thiombane, Ndeye Khady ; Gaboury, Louis ; Mader, Sylvie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-eeefd8de207dcc0c69be0351b184e47539d5d2a8618d43c21d999344f2b269ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biological markers</topic><topic>Breast cancer</topic><topic>Breast tumors</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell growth</topic><topic>Drug delivery</topic><topic>Estrogen</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>GATA-3 protein</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Medical prognosis</topic><topic>Progesterone</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Sex hormones</topic><topic>Transcription factors</topic><topic>Transcriptomes</topic><topic>Tumor cell lines</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Xenoestrogens</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Porras, Lucas</creatorcontrib><creatorcontrib>Gorse, Faustine</creatorcontrib><creatorcontrib>Thiombane, Ndeye Khady</creatorcontrib><creatorcontrib>Gaboury, Louis</creatorcontrib><creatorcontrib>Mader, Sylvie</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Porras, Lucas</au><au>Gorse, Faustine</au><au>Thiombane, Ndeye Khady</au><au>Gaboury, Louis</au><au>Mader, Sylvie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3</atitle><jtitle>Cancers</jtitle><date>2022-11-06</date><risdate>2022</risdate><volume>14</volume><issue>21</issue><spage>5453</spage><pages>5453-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR− status in ER+ tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower PGR expression, the clinical PR status does not correlate accurately with the expression of ESR1 or of ER target genes, including PGR itself. We identified carbonic anhydrase 12 (CA12) as an estrogen target gene better correlated with ESR1 than PGR, reflecting CA12 regulation by both ERα and the luminal factor and upstream ESR1 regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ER+PR− tumors expressed CAXII at levels similar to those of ER+PR+ tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ER+PR− breast cancer cell lines. The few ER−PR+ tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>36358871</pmid><doi>10.3390/cancers14215453</doi><orcidid>https://orcid.org/0000-0002-7093-8139</orcidid><orcidid>https://orcid.org/0000-0002-6423-627X</orcidid><orcidid>https://orcid.org/0000-0001-8859-6192</orcidid><orcidid>https://orcid.org/0000-0001-8392-998X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2022-11, Vol.14 (21), p.5453 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9657334 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Biological markers Breast cancer Breast tumors Cancer therapies Care and treatment Cell growth Drug delivery Estrogen Estrogen receptors Estrogens GATA-3 protein Gene expression Genes Genetic aspects Health aspects Medical prognosis Progesterone Prognosis Proteins Receptors Sex hormones Transcription factors Transcriptomes Tumor cell lines Tumorigenesis Tumors Xenoestrogens |
| title | CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T07%3A34%3A25IST&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=CAXII%20Is%20a%20Surrogate%20Marker%20for%20Luminal%20Breast%20Tumors%20Regulated%20by%20ER%20and%20GATA3&rft.jtitle=Cancers&rft.au=Porras,%20Lucas&rft.date=2022-11-06&rft.volume=14&rft.issue=21&rft.spage=5453&rft.pages=5453-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers14215453&rft_dat=%3Cgale_pubme%3EA745272426%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=2734617732&rft_id=info:pmid/36358871&rft_galeid=A745272426&rfr_iscdi=true |