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- Title
Decreased Camptothecin Sensitivity of the Stem-Cell-Like Fraction of Caco2 Cells Correlates with an Altered Phosphorylation Pattern of Topoisomerase I.
- Authors
Roy, Amit; Tesauro, Cinzia; Frøhlich, Rikke; Hede, Marianne S.; Nielsen, Maria J.; Kjeldsen, Eigil; Bonven, Bjarne; Stougaard, Magnus; Gromova, Irina; Knudsen, Birgitta R.
- Abstract
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.
- Subjects
CAMPTOTHECIN; STEM cells; PHOSPHORYLATION; DNA topoisomerase I; CD44 antigen; COLON cancer; CELL lines
- Publication
PLoS ONE, 2014, Vol 9, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0099628