EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer
Background Tamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3...
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| creator | Xie, Yu Han, Xiao Yu, Jing Yuan, Mengci Yan, Yan Qin, Junfang Lan, Lan Wang, Yue |
| description | Background
Tamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3 in tamoxifen resistance (TamR) and elucidate its molecular mechanism.
Methods
TamR cell models were established and NGS was used to screening signaling alternation. Western blot and qRT-PCR were used to analysis the expression of ERα, EGR3, MCL1 and factors associated with apoptosis. CCK8, colony formation and apoptosis assay were used to analysis resistance to Tam. Immunofluorescence, chromatin immunoprecipitation, and dual luciferase assays were used to investigate mechanism of regulation.
Results
We observed that EGR3, a deeply rooted ERα response factor, showed increased upregulation in response to both estrone (E1) and Tam in TamR cells with elevated level of E1 and ERα expression, indicating a potential connection between EGR3 and TamR. Mechanically, manipulating EGR3 expression revealed that it imparted resistance to Tam through increased expression of the downstream molecule MCL1 (apoptosis suppressor gene) that it regulated. Mechanismly, EGR3 directly binds to the promoter of the anti-apoptotic factor MCL1 gene, facilitating its transcription. Furthermore, apoptosis assays revealed that E1 reduces Tam induced apoptosis by upregulating EGR3 expression. Importantly, clinical public database confirmed the high expression of EGR3 in breast cancer tissue and in Tam-treated patients.
Conclusions
These findings shed light on the novel estrogen/EGR3/MCL1 axis and its role in inducing TamR in ER positive breast cancer. EGR3 emerges as a promising target to overcome TamR. The elucidation of this mechanism holds potential for the development of new therapeutic modalities to overcome endocrine therapy resistance in clinical settings. |
| doi_str_mv | 10.1007/s00432-023-05503-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3153548703</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3153548703</sourcerecordid><originalsourceid>FETCH-LOGICAL-c359t-43061a07818af8dbce685f486796fda96669685e0b5fd37dbedb7e8b9df63ce83</originalsourceid><addsrcrecordid>eNqFkT9vFDEQxS0EIkfgC1AgSzQ0C-Od9b8SRSFEihQJJQ2N5V2Pw0Z3drD3ovDt48sFIlFAZfvNb9549Bh7K-CjANCfKsCAfQc9diAlYKeesZXYSQJRPmcrEFp0shfqgL2q9RraW-r-JTtAba3VUqzY9-OTb8h9CpzqUnIi7gvxOd3m9S2FduHLD-KL3-S7OVLihepcF58memi6KfmqSXXOiefIx0K-Lnza1ctr9iL6daU3j-chu_xyfHH0tTs7Pzk9-nzWTSjt0g0ISnjQRhgfTRgnUkbGwShtVQzeKqVsUwhGGQPqMFIYNZnRhqhwIoOH7MPet33m57at4TZznWi99onytjoUEuVgNOB_0d5YNAMotXN9_xd6nbcltUVcb6GXVgg9NKrfU1PJtRaK7qbMG19-OQFuF5Lbh-RaSO4hJKda07tH6-24ofCn5XcqDcA9UFspXVF5mv0P23v-bJvK</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2902591174</pqid></control><display><type>article</type><title>EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Xie, Yu ; Han, Xiao ; Yu, Jing ; Yuan, Mengci ; Yan, Yan ; Qin, Junfang ; Lan, Lan ; Wang, Yue</creator><creatorcontrib>Xie, Yu ; Han, Xiao ; Yu, Jing ; Yuan, Mengci ; Yan, Yan ; Qin, Junfang ; Lan, Lan ; Wang, Yue</creatorcontrib><description>Background
Tamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3 in tamoxifen resistance (TamR) and elucidate its molecular mechanism.
Methods
TamR cell models were established and NGS was used to screening signaling alternation. Western blot and qRT-PCR were used to analysis the expression of ERα, EGR3, MCL1 and factors associated with apoptosis. CCK8, colony formation and apoptosis assay were used to analysis resistance to Tam. Immunofluorescence, chromatin immunoprecipitation, and dual luciferase assays were used to investigate mechanism of regulation.
Results
We observed that EGR3, a deeply rooted ERα response factor, showed increased upregulation in response to both estrone (E1) and Tam in TamR cells with elevated level of E1 and ERα expression, indicating a potential connection between EGR3 and TamR. Mechanically, manipulating EGR3 expression revealed that it imparted resistance to Tam through increased expression of the downstream molecule MCL1 (apoptosis suppressor gene) that it regulated. Mechanismly, EGR3 directly binds to the promoter of the anti-apoptotic factor MCL1 gene, facilitating its transcription. Furthermore, apoptosis assays revealed that E1 reduces Tam induced apoptosis by upregulating EGR3 expression. Importantly, clinical public database confirmed the high expression of EGR3 in breast cancer tissue and in Tam-treated patients.
Conclusions
These findings shed light on the novel estrogen/EGR3/MCL1 axis and its role in inducing TamR in ER positive breast cancer. EGR3 emerges as a promising target to overcome TamR. The elucidation of this mechanism holds potential for the development of new therapeutic modalities to overcome endocrine therapy resistance in clinical settings.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-023-05503-6</identifier><identifier>PMID: 37999751</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Agents, Hormonal - pharmacology ; Antineoplastic Agents, Hormonal - therapeutic use ; Apoptosis ; Breast cancer ; breast neoplasms ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cancer Research ; Cell culture ; Cell Proliferation ; Chromatin ; chromatin immunoprecipitation ; Drug Resistance, Neoplasm - genetics ; Early Growth Response Protein 3 - genetics ; Early Growth Response Protein 3 - metabolism ; Early Growth Response Protein 3 - pharmacology ; Egr-3 protein ; Endocrine therapy ; Estrogen Receptor alpha ; Estrogen receptors ; Estrogens ; Estrone ; Estrone - pharmacology ; Estrone - therapeutic use ; Female ; fluorescent antibody technique ; Gene Expression Regulation, Neoplastic ; Hematology ; Humans ; Immunofluorescence ; Immunoprecipitation ; Internal Medicine ; luciferase ; MCF-7 Cells ; Mcl-1 protein ; MCL1 gene ; Medicine ; Medicine & Public Health ; Molecular modelling ; Myeloid Cell Leukemia Sequence 1 Protein - genetics ; Myeloid Cell Leukemia Sequence 1 Protein - metabolism ; Myeloid Cell Leukemia Sequence 1 Protein - therapeutic use ; Oncology ; Patients ; suppressor genes ; Tamoxifen ; Tamoxifen - pharmacology ; Tamoxifen - therapeutic use ; therapeutics ; Western blotting</subject><ispartof>Journal of cancer research and clinical oncology, 2023-12, Vol.149 (20), p.18103-18117</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c359t-43061a07818af8dbce685f486796fda96669685e0b5fd37dbedb7e8b9df63ce83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-023-05503-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-023-05503-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37999751$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Yu</creatorcontrib><creatorcontrib>Han, Xiao</creatorcontrib><creatorcontrib>Yu, Jing</creatorcontrib><creatorcontrib>Yuan, Mengci</creatorcontrib><creatorcontrib>Yan, Yan</creatorcontrib><creatorcontrib>Qin, Junfang</creatorcontrib><creatorcontrib>Lan, Lan</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><title>EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Background
Tamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3 in tamoxifen resistance (TamR) and elucidate its molecular mechanism.
Methods
TamR cell models were established and NGS was used to screening signaling alternation. Western blot and qRT-PCR were used to analysis the expression of ERα, EGR3, MCL1 and factors associated with apoptosis. CCK8, colony formation and apoptosis assay were used to analysis resistance to Tam. Immunofluorescence, chromatin immunoprecipitation, and dual luciferase assays were used to investigate mechanism of regulation.
Results
We observed that EGR3, a deeply rooted ERα response factor, showed increased upregulation in response to both estrone (E1) and Tam in TamR cells with elevated level of E1 and ERα expression, indicating a potential connection between EGR3 and TamR. Mechanically, manipulating EGR3 expression revealed that it imparted resistance to Tam through increased expression of the downstream molecule MCL1 (apoptosis suppressor gene) that it regulated. Mechanismly, EGR3 directly binds to the promoter of the anti-apoptotic factor MCL1 gene, facilitating its transcription. Furthermore, apoptosis assays revealed that E1 reduces Tam induced apoptosis by upregulating EGR3 expression. Importantly, clinical public database confirmed the high expression of EGR3 in breast cancer tissue and in Tam-treated patients.
Conclusions
These findings shed light on the novel estrogen/EGR3/MCL1 axis and its role in inducing TamR in ER positive breast cancer. EGR3 emerges as a promising target to overcome TamR. The elucidation of this mechanism holds potential for the development of new therapeutic modalities to overcome endocrine therapy resistance in clinical settings.</description><subject>Antineoplastic Agents, Hormonal - pharmacology</subject><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>breast neoplasms</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer Research</subject><subject>Cell culture</subject><subject>Cell Proliferation</subject><subject>Chromatin</subject><subject>chromatin immunoprecipitation</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Early Growth Response Protein 3 - genetics</subject><subject>Early Growth Response Protein 3 - metabolism</subject><subject>Early Growth Response Protein 3 - pharmacology</subject><subject>Egr-3 protein</subject><subject>Endocrine therapy</subject><subject>Estrogen Receptor alpha</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Estrone</subject><subject>Estrone - pharmacology</subject><subject>Estrone - therapeutic use</subject><subject>Female</subject><subject>fluorescent antibody technique</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunoprecipitation</subject><subject>Internal Medicine</subject><subject>luciferase</subject><subject>MCF-7 Cells</subject><subject>Mcl-1 protein</subject><subject>MCL1 gene</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular modelling</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - genetics</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - metabolism</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - therapeutic use</subject><subject>Oncology</subject><subject>Patients</subject><subject>suppressor genes</subject><subject>Tamoxifen</subject><subject>Tamoxifen - pharmacology</subject><subject>Tamoxifen - therapeutic use</subject><subject>therapeutics</subject><subject>Western blotting</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkT9vFDEQxS0EIkfgC1AgSzQ0C-Od9b8SRSFEihQJJQ2N5V2Pw0Z3drD3ovDt48sFIlFAZfvNb9549Bh7K-CjANCfKsCAfQc9diAlYKeesZXYSQJRPmcrEFp0shfqgL2q9RraW-r-JTtAba3VUqzY9-OTb8h9CpzqUnIi7gvxOd3m9S2FduHLD-KL3-S7OVLihepcF58memi6KfmqSXXOiefIx0K-Lnza1ctr9iL6daU3j-chu_xyfHH0tTs7Pzk9-nzWTSjt0g0ISnjQRhgfTRgnUkbGwShtVQzeKqVsUwhGGQPqMFIYNZnRhqhwIoOH7MPet33m57at4TZznWi99onytjoUEuVgNOB_0d5YNAMotXN9_xd6nbcltUVcb6GXVgg9NKrfU1PJtRaK7qbMG19-OQFuF5Lbh-RaSO4hJKda07tH6-24ofCn5XcqDcA9UFspXVF5mv0P23v-bJvK</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Xie, Yu</creator><creator>Han, Xiao</creator><creator>Yu, Jing</creator><creator>Yuan, Mengci</creator><creator>Yan, Yan</creator><creator>Qin, Junfang</creator><creator>Lan, Lan</creator><creator>Wang, Yue</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20231201</creationdate><title>EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer</title><author>Xie, Yu ; Han, Xiao ; Yu, Jing ; Yuan, Mengci ; Yan, Yan ; Qin, Junfang ; Lan, Lan ; Wang, Yue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-43061a07818af8dbce685f486796fda96669685e0b5fd37dbedb7e8b9df63ce83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Agents, Hormonal - pharmacology</topic><topic>Antineoplastic Agents, Hormonal - therapeutic use</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>breast neoplasms</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cancer Research</topic><topic>Cell culture</topic><topic>Cell Proliferation</topic><topic>Chromatin</topic><topic>chromatin immunoprecipitation</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Early Growth Response Protein 3 - genetics</topic><topic>Early Growth Response Protein 3 - metabolism</topic><topic>Early Growth Response Protein 3 - pharmacology</topic><topic>Egr-3 protein</topic><topic>Endocrine therapy</topic><topic>Estrogen Receptor alpha</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Estrone</topic><topic>Estrone - pharmacology</topic><topic>Estrone - therapeutic use</topic><topic>Female</topic><topic>fluorescent antibody technique</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunoprecipitation</topic><topic>Internal Medicine</topic><topic>luciferase</topic><topic>MCF-7 Cells</topic><topic>Mcl-1 protein</topic><topic>MCL1 gene</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular modelling</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein - genetics</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein - metabolism</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein - therapeutic use</topic><topic>Oncology</topic><topic>Patients</topic><topic>suppressor genes</topic><topic>Tamoxifen</topic><topic>Tamoxifen - pharmacology</topic><topic>Tamoxifen - therapeutic use</topic><topic>therapeutics</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Yu</creatorcontrib><creatorcontrib>Han, Xiao</creatorcontrib><creatorcontrib>Yu, Jing</creatorcontrib><creatorcontrib>Yuan, Mengci</creatorcontrib><creatorcontrib>Yan, Yan</creatorcontrib><creatorcontrib>Qin, Junfang</creatorcontrib><creatorcontrib>Lan, Lan</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Yu</au><au>Han, Xiao</au><au>Yu, Jing</au><au>Yuan, Mengci</au><au>Yan, Yan</au><au>Qin, Junfang</au><au>Lan, Lan</au><au>Wang, Yue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>149</volume><issue>20</issue><spage>18103</spage><epage>18117</epage><pages>18103-18117</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Background
Tamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3 in tamoxifen resistance (TamR) and elucidate its molecular mechanism.
Methods
TamR cell models were established and NGS was used to screening signaling alternation. Western blot and qRT-PCR were used to analysis the expression of ERα, EGR3, MCL1 and factors associated with apoptosis. CCK8, colony formation and apoptosis assay were used to analysis resistance to Tam. Immunofluorescence, chromatin immunoprecipitation, and dual luciferase assays were used to investigate mechanism of regulation.
Results
We observed that EGR3, a deeply rooted ERα response factor, showed increased upregulation in response to both estrone (E1) and Tam in TamR cells with elevated level of E1 and ERα expression, indicating a potential connection between EGR3 and TamR. Mechanically, manipulating EGR3 expression revealed that it imparted resistance to Tam through increased expression of the downstream molecule MCL1 (apoptosis suppressor gene) that it regulated. Mechanismly, EGR3 directly binds to the promoter of the anti-apoptotic factor MCL1 gene, facilitating its transcription. Furthermore, apoptosis assays revealed that E1 reduces Tam induced apoptosis by upregulating EGR3 expression. Importantly, clinical public database confirmed the high expression of EGR3 in breast cancer tissue and in Tam-treated patients.
Conclusions
These findings shed light on the novel estrogen/EGR3/MCL1 axis and its role in inducing TamR in ER positive breast cancer. EGR3 emerges as a promising target to overcome TamR. The elucidation of this mechanism holds potential for the development of new therapeutic modalities to overcome endocrine therapy resistance in clinical settings.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37999751</pmid><doi>10.1007/s00432-023-05503-6</doi><tpages>15</tpages></addata></record> |
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| subjects | Antineoplastic Agents, Hormonal - pharmacology Antineoplastic Agents, Hormonal - therapeutic use Apoptosis Breast cancer breast neoplasms Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Cancer Research Cell culture Cell Proliferation Chromatin chromatin immunoprecipitation Drug Resistance, Neoplasm - genetics Early Growth Response Protein 3 - genetics Early Growth Response Protein 3 - metabolism Early Growth Response Protein 3 - pharmacology Egr-3 protein Endocrine therapy Estrogen Receptor alpha Estrogen receptors Estrogens Estrone Estrone - pharmacology Estrone - therapeutic use Female fluorescent antibody technique Gene Expression Regulation, Neoplastic Hematology Humans Immunofluorescence Immunoprecipitation Internal Medicine luciferase MCF-7 Cells Mcl-1 protein MCL1 gene Medicine Medicine & Public Health Molecular modelling Myeloid Cell Leukemia Sequence 1 Protein - genetics Myeloid Cell Leukemia Sequence 1 Protein - metabolism Myeloid Cell Leukemia Sequence 1 Protein - therapeutic use Oncology Patients suppressor genes Tamoxifen Tamoxifen - pharmacology Tamoxifen - therapeutic use therapeutics Western blotting |
| title | EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer |
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