Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2138454 | Leukemia Research | 2010 | 7 Pages |
Abstract
Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE2 to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE2–cAMP–PKC-mediated pathway.
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Authors
Arunasree M. Kalle, Sachchidanand Sachchidanand, Reddanna Pallu,