The effect of telomerase template antagonist GRN163L on Bone-Marrow-Derived rat mMesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6

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dc.citation.epage233en_US
dc.citation.issueNumber2en_US
dc.citation.spage224en_US
dc.citation.volumeNumber6en_US
dc.contributor.authorTokcaer-Keskin, Z.en_US
dc.contributor.authorDikmen, Z. G.en_US
dc.contributor.authorAyaloglu-Butun, F.en_US
dc.contributor.authorGultekin, S.en_US
dc.contributor.authorGryaznov, S. M.en_US
dc.contributor.authorAkcali, K. C.en_US
dc.date.accessioned2016-02-08T09:58:27Z
dc.date.available2016-02-08T09:58:27Z
dc.date.issued2010en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractTelomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. The telomerase inhibitor GRN163L, was shown to inhibit the growth of cancer cells both in vitro and in vivo. Mesenchymal stem cells (MSCs) also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. MSCs are multipotent cells and are important for the homeostasis of the organism. In this study, we sought to demonstrate in vitro effects of GRN163L on rat MSCs. When MSCs were treated with 1 μM GRN163L, their phenotype changed from spindle-shaped cells to rounded ones and detached from the plate surface, similar to cancer cells. Quantitative-RT-PCR and immunoblotting results revealed that GRN163L holds MSCs at the G1 state of the cell cycle, with a drastic decrease in mRNA and protein levels of cyclin D1 and its cdk counterparts, cdk4 and cdk6. This effect was not observed when MSCs were treated with a mismatch control oligonucleotide. One week after GRN163L was removed, mRNA and protein expressions of the genes, as well as the phenotype of MSCs returned to those of untreated cells. Therefore, we concluded that GRN163L does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions. Our study provides additional support for treating cancers by administrating GRN163L without depleting the body's stem cell pools. © 2010 Springer Science+Business Media, LLC.en_US
dc.identifier.doi10.1007/s12015-010-9124-7en_US
dc.identifier.issn1550-8943
dc.identifier.urihttp://hdl.handle.net/11693/22313
dc.language.isoEnglishen_US
dc.publisherSpringer Science+Business Mediaen_US
dc.relation.isversionofhttp://dx.doi.org/10.1007/s12015-010-9124-7en_US
dc.source.titleStem Cell Reviews and Reportsen_US
dc.subjectCdk4en_US
dc.subjectCdk6en_US
dc.subjectCyclin D1en_US
dc.subjectGRN163Len_US
dc.subjectMesenchymal stem cellsen_US
dc.subjectTelomeraseen_US
dc.subjectCdk4 protein, raten_US
dc.subjectCdk6 protein, mouseen_US
dc.subjectCyclin D1en_US
dc.subjectCyclin dependent kinase 4en_US
dc.subjectCyclin dependent kinase 6en_US
dc.subjectGRN163L peptideen_US
dc.subjectOligonucleotideen_US
dc.subjectTelomeraseen_US
dc.titleThe effect of telomerase template antagonist GRN163L on Bone-Marrow-Derived rat mMesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6en_US
dc.typeArticleen_US

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