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Decreased Camptothecin Sensitivity of the Stem-Cell-Like Fraction of Caco2 Cells Correlates with an Altered Phosphorylation Pattern of Topoisomerase I

The CD44+ and CD44− subpopulations of the colorectal cancer cell line Caco2 were analyzed separately for their sensitivities to the antitumor drug camptothecin. CD44+ cells were less sensitive to camptothecin than CD44− cells. The relative resistance of CD44+ cells was correlated with (i) reduced ac...

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Detalles Bibliográficos
Autores principales: Roy, Amit, Tesauro, Cinzia, Frøhlich, Rikke, Hede, Marianne S., Nielsen, Maria J., Kjeldsen, Eigil, Bonven, Bjarne, Stougaard, Magnus, Gromova, Irina, Knudsen, Birgitta R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069021/
https://www.ncbi.nlm.nih.gov/pubmed/24960044
http://dx.doi.org/10.1371/journal.pone.0099628
Descripción
Sumario:The CD44+ and CD44− subpopulations of the colorectal cancer cell line Caco2 were analyzed separately for their sensitivities to the antitumor drug camptothecin. CD44+ cells were less sensitive to camptothecin than CD44− cells. The relative resistance of CD44+ cells was correlated with (i) reduced activity of the nuclear enzyme topoisomerase I and (ii) insensitivity of this enzyme to camptothecin when analyzed in extracts. In contrast, topoisomerase I activity was higher in extracts from CD44− cells and the enzyme was camptothecin sensitive. Topoisomerase I from the two subpopulations were differentially phosphorylated in a manner that appeared to determine the drug sensitivity and activity of the enzyme. This finding was further supported by the fact that phosphorylation of topoisomerase I in CD44+ cell extract by protein kinase CK2 converted the enzyme to a camptothecin sensitive, more active form mimicking topoisomerase I in extracts from CD44− cells. Conversely, dephosphorylation of topoisomerase I in extracts from CD44− cells rendered the enzyme less active and camptothecin resistant. These findings add to our understanding of chemotherapy resistance in the Caco2 CD44+ cancer stem cell model.