Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability
Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the network associated with tumor initiation and metastasis....
Gespeichert in:
| Veröffentlicht in: | International journal of molecular sciences 2023-05, Vol.24 (11), p.9142 |
|---|---|
| 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 | 11 |
| container_start_page | 9142 |
| container_title | International journal of molecular sciences |
| container_volume | 24 |
| creator | Rajan, Robin G Krutilina, Raisa I Ignatova, Tatyana N Pavicevich, Zoran S Dulatova, Galina M Lane, Maria A Chatterjee, Arindam R Rooney, Robert J Antony, Mymoon Hagerty, Vivian R Kukekov, Nickolay V Hanafy, Khalid A Vrionis, Frank D |
| description | Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the
network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including
and
were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of
and
genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus,
transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity. |
| doi_str_mv | 10.3390/ijms24119142 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10252816</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A752740488</galeid><sourcerecordid>A752740488</sourcerecordid><originalsourceid>FETCH-LOGICAL-c480t-eee082796326bc9ee3cfb2e572b0ea43c4303902325f2a751af2e471345ab74d3</originalsourceid><addsrcrecordid>eNptkk1vEzEQhlcIREvhxhlZ4sKBtP7aXe8JpeErUqFItFytWe9s4rCxU9tL1P_Aj8ahpaQIWbJHnud97RlNUTxn9FiIhp7Y1TpyyVjDJH9QHOadTyit6od78UHxJMYVpVzwsnlcHIiaN4o27LD4ebkJuBgHSNY74nuSlkjOTRInknzGtPXhO7GOnEKEgZwGhJjIDJzBQOaRTGP0xkLCjmxtWpJ5iuQTpgxlP0O--IQu2awE15GvS7-N5MLGOCJ5ixt0Xc6SbxAstHaw6fpp8aiHIeKz2_OouHz_7mL2cXJ2_mE-m55NjFQ0TRCRKl43leBVaxpEYfqWY1nzliJIYaSguTO7YnsOdcmg5yhrJmQJbS07cVS8ufHdjO0aO5O_EWDQm2DXEK61B6vvZ5xd6oX_oRnlJVesyg6vbh2CvxoxJr220eAwgEM_Rs0Vl5VqKsUy-vIfdOXH4HJ9vylKVcOrv9QCBtTW9T4_bHamelqXvJZUKpWp4_9QeXW4tsY77G2-vyd4fSMwwccYsL8rklG9Gx-9Pz4Zf7HfmDv4z7yIXzMGwEU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2824008926</pqid></control><display><type>article</type><title>Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Rajan, Robin G ; Krutilina, Raisa I ; Ignatova, Tatyana N ; Pavicevich, Zoran S ; Dulatova, Galina M ; Lane, Maria A ; Chatterjee, Arindam R ; Rooney, Robert J ; Antony, Mymoon ; Hagerty, Vivian R ; Kukekov, Nickolay V ; Hanafy, Khalid A ; Vrionis, Frank D</creator><creatorcontrib>Rajan, Robin G ; Krutilina, Raisa I ; Ignatova, Tatyana N ; Pavicevich, Zoran S ; Dulatova, Galina M ; Lane, Maria A ; Chatterjee, Arindam R ; Rooney, Robert J ; Antony, Mymoon ; Hagerty, Vivian R ; Kukekov, Nickolay V ; Hanafy, Khalid A ; Vrionis, Frank D</creatorcontrib><description>Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the
network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including
and
were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of
and
genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus,
transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24119142</identifier><identifier>PMID: 37298091</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Brain tumors ; Breast cancer ; Breast Neoplasms - metabolism ; c-Myc protein ; CD44 antigen ; Cell culture ; Cell Line, Tumor ; Cloning ; Development and progression ; Dkk1 protein ; DNA binding proteins ; Drug resistance ; Efficiency ; Epigenetics ; Female ; Flow cytometry ; Gelatinase B ; Genes ; Genotype & phenotype ; Heterogeneity ; Humans ; Lesions ; Metastases ; Metastasis ; Metastatic seeding ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Myc protein ; Neoplastic Stem Cells - metabolism ; Oct-4 protein ; Paclitaxel ; Paclitaxel - metabolism ; Paclitaxel - pharmacology ; Prognosis ; Stem cells ; Transcription factors ; Transcriptomes ; Triple Negative Breast Neoplasms - pathology ; Tumors ; Two dimensional flow ; Up-Regulation ; Variability</subject><ispartof>International journal of molecular sciences, 2023-05, Vol.24 (11), p.9142</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 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>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-eee082796326bc9ee3cfb2e572b0ea43c4303902325f2a751af2e471345ab74d3</citedby><cites>FETCH-LOGICAL-c480t-eee082796326bc9ee3cfb2e572b0ea43c4303902325f2a751af2e471345ab74d3</cites><orcidid>0000-0002-2118-4019 ; 0000-0002-6172-2010</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/PMC10252816/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252816/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37298091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rajan, Robin G</creatorcontrib><creatorcontrib>Krutilina, Raisa I</creatorcontrib><creatorcontrib>Ignatova, Tatyana N</creatorcontrib><creatorcontrib>Pavicevich, Zoran S</creatorcontrib><creatorcontrib>Dulatova, Galina M</creatorcontrib><creatorcontrib>Lane, Maria A</creatorcontrib><creatorcontrib>Chatterjee, Arindam R</creatorcontrib><creatorcontrib>Rooney, Robert J</creatorcontrib><creatorcontrib>Antony, Mymoon</creatorcontrib><creatorcontrib>Hagerty, Vivian R</creatorcontrib><creatorcontrib>Kukekov, Nickolay V</creatorcontrib><creatorcontrib>Hanafy, Khalid A</creatorcontrib><creatorcontrib>Vrionis, Frank D</creatorcontrib><title>Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the
network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including
and
were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of
and
genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus,
transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.</description><subject>Animals</subject><subject>Brain tumors</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>c-Myc protein</subject><subject>CD44 antigen</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Cloning</subject><subject>Development and progression</subject><subject>Dkk1 protein</subject><subject>DNA binding proteins</subject><subject>Drug resistance</subject><subject>Efficiency</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Gelatinase B</subject><subject>Genes</subject><subject>Genotype & phenotype</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Lesions</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Metastatic seeding</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Myc protein</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Oct-4 protein</subject><subject>Paclitaxel</subject><subject>Paclitaxel - metabolism</subject><subject>Paclitaxel - pharmacology</subject><subject>Prognosis</subject><subject>Stem cells</subject><subject>Transcription factors</subject><subject>Transcriptomes</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Tumors</subject><subject>Two dimensional flow</subject><subject>Up-Regulation</subject><subject>Variability</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</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>eNptkk1vEzEQhlcIREvhxhlZ4sKBtP7aXe8JpeErUqFItFytWe9s4rCxU9tL1P_Aj8ahpaQIWbJHnud97RlNUTxn9FiIhp7Y1TpyyVjDJH9QHOadTyit6od78UHxJMYVpVzwsnlcHIiaN4o27LD4ebkJuBgHSNY74nuSlkjOTRInknzGtPXhO7GOnEKEgZwGhJjIDJzBQOaRTGP0xkLCjmxtWpJ5iuQTpgxlP0O--IQu2awE15GvS7-N5MLGOCJ5ixt0Xc6SbxAstHaw6fpp8aiHIeKz2_OouHz_7mL2cXJ2_mE-m55NjFQ0TRCRKl43leBVaxpEYfqWY1nzliJIYaSguTO7YnsOdcmg5yhrJmQJbS07cVS8ufHdjO0aO5O_EWDQm2DXEK61B6vvZ5xd6oX_oRnlJVesyg6vbh2CvxoxJr220eAwgEM_Rs0Vl5VqKsUy-vIfdOXH4HJ9vylKVcOrv9QCBtTW9T4_bHamelqXvJZUKpWp4_9QeXW4tsY77G2-vyd4fSMwwccYsL8rklG9Gx-9Pz4Zf7HfmDv4z7yIXzMGwEU</recordid><startdate>20230523</startdate><enddate>20230523</enddate><creator>Rajan, Robin G</creator><creator>Krutilina, Raisa I</creator><creator>Ignatova, Tatyana N</creator><creator>Pavicevich, Zoran S</creator><creator>Dulatova, Galina M</creator><creator>Lane, Maria A</creator><creator>Chatterjee, Arindam R</creator><creator>Rooney, Robert J</creator><creator>Antony, Mymoon</creator><creator>Hagerty, Vivian R</creator><creator>Kukekov, Nickolay V</creator><creator>Hanafy, Khalid A</creator><creator>Vrionis, Frank D</creator><general>MDPI AG</general><general>MDPI</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>7X7</scope><scope>7XB</scope><scope>88E</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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</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/0000-0002-2118-4019</orcidid><orcidid>https://orcid.org/0000-0002-6172-2010</orcidid></search><sort><creationdate>20230523</creationdate><title>Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability</title><author>Rajan, Robin G ; Krutilina, Raisa I ; Ignatova, Tatyana N ; Pavicevich, Zoran S ; Dulatova, Galina M ; Lane, Maria A ; Chatterjee, Arindam R ; Rooney, Robert J ; Antony, Mymoon ; Hagerty, Vivian R ; Kukekov, Nickolay V ; Hanafy, Khalid A ; Vrionis, Frank D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-eee082796326bc9ee3cfb2e572b0ea43c4303902325f2a751af2e471345ab74d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Brain tumors</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>c-Myc protein</topic><topic>CD44 antigen</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Cloning</topic><topic>Development and progression</topic><topic>Dkk1 protein</topic><topic>DNA binding proteins</topic><topic>Drug resistance</topic><topic>Efficiency</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Gelatinase B</topic><topic>Genes</topic><topic>Genotype & phenotype</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Lesions</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Metastatic seeding</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Myc protein</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Oct-4 protein</topic><topic>Paclitaxel</topic><topic>Paclitaxel - metabolism</topic><topic>Paclitaxel - pharmacology</topic><topic>Prognosis</topic><topic>Stem cells</topic><topic>Transcription factors</topic><topic>Transcriptomes</topic><topic>Triple Negative Breast Neoplasms - pathology</topic><topic>Tumors</topic><topic>Two dimensional flow</topic><topic>Up-Regulation</topic><topic>Variability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rajan, Robin G</creatorcontrib><creatorcontrib>Krutilina, Raisa I</creatorcontrib><creatorcontrib>Ignatova, Tatyana N</creatorcontrib><creatorcontrib>Pavicevich, Zoran S</creatorcontrib><creatorcontrib>Dulatova, Galina M</creatorcontrib><creatorcontrib>Lane, Maria A</creatorcontrib><creatorcontrib>Chatterjee, Arindam R</creatorcontrib><creatorcontrib>Rooney, Robert J</creatorcontrib><creatorcontrib>Antony, Mymoon</creatorcontrib><creatorcontrib>Hagerty, Vivian R</creatorcontrib><creatorcontrib>Kukekov, Nickolay V</creatorcontrib><creatorcontrib>Hanafy, Khalid A</creatorcontrib><creatorcontrib>Vrionis, Frank D</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>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>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>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rajan, Robin G</au><au>Krutilina, Raisa I</au><au>Ignatova, Tatyana N</au><au>Pavicevich, Zoran S</au><au>Dulatova, Galina M</au><au>Lane, Maria A</au><au>Chatterjee, Arindam R</au><au>Rooney, Robert J</au><au>Antony, Mymoon</au><au>Hagerty, Vivian R</au><au>Kukekov, Nickolay V</au><au>Hanafy, Khalid A</au><au>Vrionis, Frank D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-05-23</date><risdate>2023</risdate><volume>24</volume><issue>11</issue><spage>9142</spage><pages>9142-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the
network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including
and
were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of
and
genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus,
transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37298091</pmid><doi>10.3390/ijms24119142</doi><orcidid>https://orcid.org/0000-0002-2118-4019</orcidid><orcidid>https://orcid.org/0000-0002-6172-2010</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2023-05, Vol.24 (11), p.9142 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10252816 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Brain tumors Breast cancer Breast Neoplasms - metabolism c-Myc protein CD44 antigen Cell culture Cell Line, Tumor Cloning Development and progression Dkk1 protein DNA binding proteins Drug resistance Efficiency Epigenetics Female Flow cytometry Gelatinase B Genes Genotype & phenotype Heterogeneity Humans Lesions Metastases Metastasis Metastatic seeding Mice Mice, Inbred NOD Mice, SCID Myc protein Neoplastic Stem Cells - metabolism Oct-4 protein Paclitaxel Paclitaxel - metabolism Paclitaxel - pharmacology Prognosis Stem cells Transcription factors Transcriptomes Triple Negative Breast Neoplasms - pathology Tumors Two dimensional flow Up-Regulation Variability |
| title | Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T22%3A04%3A48IST&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=Upregulation%20of%20the%20Oct3/4%20Network%20in%20Basal%20Breast%20Cancer%20Is%20Associated%20with%20Its%20Metastatic%20Potential%20and%20Shows%20Tissue%20Dependent%20Variability&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Rajan,%20Robin%20G&rft.date=2023-05-23&rft.volume=24&rft.issue=11&rft.spage=9142&rft.pages=9142-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms24119142&rft_dat=%3Cgale_pubme%3EA752740488%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=2824008926&rft_id=info:pmid/37298091&rft_galeid=A752740488&rfr_iscdi=true |