The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential
The striking similarity displayed at the mechanistic level between tumorigenesis and the generation of induced pluripotent stem cells and the fact that genes and pathways relevant for embryonic development are reactivated during tumor progression highlights the link between pluripotency and cancer....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00308/full |
| _version_ | 1828485776204103680 |
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| author | Juan Manuel eIglesias Juan Manuel eIglesias Olatz eLeis Esnaola Olatz eLeis Esnaola Estibaliz ePerez Ruiz Juan eGumuzio Barrie Juan eGumuzio Barrie Francisco eGarcia Garcia Francisco eGarcia Garcia Ariane eAduriz Izaskun eBeloqui Susana eHernandez Garcia Maria Paz eLopez Mato Joaquin eDopazo Joaquin eDopazo Joaquin eDopazo Atanasio ePandiella Javier eMenendez Javier eMenendez Angel eGarcia Martin Angel eGarcia Martin |
| author_facet | Juan Manuel eIglesias Juan Manuel eIglesias Olatz eLeis Esnaola Olatz eLeis Esnaola Estibaliz ePerez Ruiz Juan eGumuzio Barrie Juan eGumuzio Barrie Francisco eGarcia Garcia Francisco eGarcia Garcia Ariane eAduriz Izaskun eBeloqui Susana eHernandez Garcia Maria Paz eLopez Mato Joaquin eDopazo Joaquin eDopazo Joaquin eDopazo Atanasio ePandiella Javier eMenendez Javier eMenendez Angel eGarcia Martin Angel eGarcia Martin |
| author_sort | Juan Manuel eIglesias |
| collection | DOAJ |
| description | The striking similarity displayed at the mechanistic level between tumorigenesis and the generation of induced pluripotent stem cells and the fact that genes and pathways relevant for embryonic development are reactivated during tumor progression highlights the link between pluripotency and cancer. Based on these observations we tested whether it is possible to use a pluripotency-associated transcriptional reporter, whose activation is driven by the SRR2 enhancer from the Sox2 gene promoter (named S4+ reporter), to isolate cancer stem cells from breast cancer cell lines. The S4+ pluripotency transcriptional reporter allows the isolation of cells with enhanced tumorigenic potential and its activation was switched on and off in the cell lines studied, reflecting a plastic cellular process. Microarray analysis comparing the populations in which the reporter construct is active vs. inactive showed that positive cells expressed higher mRNA levels of cytokines (IL-8, IL-6, TNF) and genes (such as ATF3, SNAI2, KLF6) previously related with the cancer stem cell phenotype in breast cancer. |
| first_indexed | 2024-12-11T09:21:24Z |
| format | Article |
| id | doaj.art-608e08bac19242ce834cc78d863168e8 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T09:21:24Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-608e08bac19242ce834cc78d863168e82022-12-22T01:13:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2014-11-01410.3389/fonc.2014.00308111782The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potentialJuan Manuel eIglesias0Juan Manuel eIglesias1Olatz eLeis Esnaola2Olatz eLeis Esnaola3Estibaliz ePerez Ruiz4Juan eGumuzio Barrie5Juan eGumuzio Barrie6Francisco eGarcia Garcia7Francisco eGarcia Garcia8Ariane eAduriz9Izaskun eBeloqui10Susana eHernandez Garcia11Maria Paz eLopez Mato12Joaquin eDopazo13Joaquin eDopazo14Joaquin eDopazo15Atanasio ePandiella16Javier eMenendez17Javier eMenendez18Angel eGarcia Martin19Angel eGarcia Martin20Synpromics LtdFundacion InbiomedStemTek TherapeuticsFundacion InbiomedFundacion InbiomedStemTek TherapeuticsFundacion InbiomedCentro de Investigacion Principe FelipeCentro de Investigacion Principe felipeFundacion InbiomedFundacion InbiomedInstituto de Biología Molecular y Celular del CancerFundacion InbiomedCentro de Investigacion Principe FelipeCentro de Investigacion Principe felipeCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)Instituto de Biología Molecular y Celular del CancerCatalan Institute of OncologyGirona Biomedical Research Institute (IDIBGi)StemTek TherapeuticsFundacion InbiomedThe striking similarity displayed at the mechanistic level between tumorigenesis and the generation of induced pluripotent stem cells and the fact that genes and pathways relevant for embryonic development are reactivated during tumor progression highlights the link between pluripotency and cancer. Based on these observations we tested whether it is possible to use a pluripotency-associated transcriptional reporter, whose activation is driven by the SRR2 enhancer from the Sox2 gene promoter (named S4+ reporter), to isolate cancer stem cells from breast cancer cell lines. The S4+ pluripotency transcriptional reporter allows the isolation of cells with enhanced tumorigenic potential and its activation was switched on and off in the cell lines studied, reflecting a plastic cellular process. Microarray analysis comparing the populations in which the reporter construct is active vs. inactive showed that positive cells expressed higher mRNA levels of cytokines (IL-8, IL-6, TNF) and genes (such as ATF3, SNAI2, KLF6) previously related with the cancer stem cell phenotype in breast cancer.http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00308/fullStem CellsEMTreporterSOX2pluripotencybreast cancer stem cell |
| spellingShingle | Juan Manuel eIglesias Juan Manuel eIglesias Olatz eLeis Esnaola Olatz eLeis Esnaola Estibaliz ePerez Ruiz Juan eGumuzio Barrie Juan eGumuzio Barrie Francisco eGarcia Garcia Francisco eGarcia Garcia Ariane eAduriz Izaskun eBeloqui Susana eHernandez Garcia Maria Paz eLopez Mato Joaquin eDopazo Joaquin eDopazo Joaquin eDopazo Atanasio ePandiella Javier eMenendez Javier eMenendez Angel eGarcia Martin Angel eGarcia Martin The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential Frontiers in Oncology Stem Cells EMT reporter SOX2 pluripotency breast cancer stem cell |
| title | The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| title_full | The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| title_fullStr | The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| title_full_unstemmed | The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| title_short | The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| title_sort | activation of the sox2 rr2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential |
| topic | Stem Cells EMT reporter SOX2 pluripotency breast cancer stem cell |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00308/full |
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