MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression

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dc.contributor.authorOliver, Jaime A.en_US
dc.contributor.authorORTIZ, Rau´ Len_US
dc.contributor.authorNez-Luna, Cristina Jimeen_US
dc.contributor.authorCabeza, Lauraen_US
dc.contributor.authorPerazzoli, Gloriaen_US
dc.contributor.authorCaba, Octavioen_US
dc.contributor.authorMesas, Cristinaen_US
dc.contributor.authorMelguizo, Consolacio´ Nen_US
dc.contributor.authorPrados, Joseen_US
dc.date.accessioned2020-11-18T10:14:15Z
dc.date.available2020-11-18T10:14:15Z
dc.date.issued2020-09
dc.description.abstractCancer stem cells (CSCs) from colorectal cancer (CRC), characterized by CD133 expression, have beenassociated with 5-fluorouracile (5-FU) chemoresistance. DNA repair mechanisms, such as O6-alkylguanineDNA alkyltransferase (MGMT) and mismatch repair (MMR) systems, have also been correlated to 5-FUresistance in CRC. The aim of this study was to evaluate the modulation of CD133 and MGMT in MMRproficient and MMR-deficient CRC cells under 5-FU treatment and the effect of this drug in CSCs. CD133 andMGMT methylation status were determined in MMR-proficient (SW480 and HT29) and MMR-deficient (RKOand HCT116) cell lines by methylation-specific PCRs. SW480 and RKO were selected to determine modulation of CD133, MGMT and MMR expression after 5-FU treatment by qPCR. In addition, CD133, MGMTand MMR were analyze in SW480 and RKO CSCs. No association between promoter methylation and MGMTand CD133 expression was found. 5-FU treatment increased CD133 expression independently to MMR statusin SW480 and RKO and was able to increase hMLH1 expression in RKO, a MMR-deficient cell line. RKO/CSCs overexpressed CD133 and MMR (hMSH2 and hMSH6) while SW480/CSCs showed a significantincrease in CD133, MMR (hMLH1, hMSH2 and hMSH6) and MGMT, moreover 5-FU resistance thanparental cell lines. Thus, although CSCs 5-FU chemoresistance appears to be independently to MMR status,hMLH1 might play a key role in CSC response to 5-FU. New drugs exploding these differences could benefitthe prognostic of patients with CRC.en_US
dc.identifier.affiliationsCenter for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UKen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerlanden_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Medicine, University of Almeria, 04120 Almerı´a, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.affiliationsInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spainen_US
dc.identifier.affiliationsDepartment of Anatomy and Embryology, University of Granada, Granada, Spainen_US
dc.identifier.affiliationsBiosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spainen_US
dc.identifier.citationOliver Jaime A., Ortiz Rau´ L, Nez-Luna Cristina Jime, Cabeza Laura, Perazzoli Gloria, Caba Octavio, Mesas Cristina, Melguizo Consolacio´ N, Prados Jose. MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression. Journal of Biosciences. 2020 Sep; : 1-9en_US
dc.identifier.issn0250-5991
dc.identifier.issn0973-7138
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/214234
dc.languageenen_US
dc.publisherIndian Academy of Sciencesen_US
dc.relation.volume45en_US
dc.source.urihttps://dx.doi.org//10.1007/s12038-020-00093-8en_US
dc.subjectCancer stem cellsen_US
dc.subjectCD133en_US
dc.subjectcolorectal canceren_US
dc.subject5-fluorouracilen_US
dc.subjectMGMTen_US
dc.subjectMMRen_US
dc.titleMMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expressionen_US
dc.typeJournal Articleen_US
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