@article{92836, author = {Schaar and Lui and Sharma and Ting and Martin and Krier and Ciardella and Osman and Goodell and Daniel Notterman and Strair}, title = {12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase expression and AML cell survival.}, abstract = {

12-O-Tetradecanoylphorbol-13-acetate (TPA) is being developed as a therapeutic agent by virtue of its being a potent modulator of signal transduction in pre-clinical models of AML [Strair RK, Schaar D, Goodell L, Aisner J, Chin KV, Eid J, et al. Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate. Clin Cancer Res 2002;8:2512-8]. In this report, we identify a subset of primary AML samples that undergoes apoptosis after exposure to TPA and demonstrate that TPA-induced cytotoxicity is associated with modulation of the ERK signaling pathway. Analysis of mitogen-activated protein kinase (MAPK) dual-specificity phosphatases (DUSP), as potential regulators of AML cell signaling, indicates that these genes are coordinately regulated and rapidly induced by TPA in primary AML cells. Therefore, TPA-induced primary AML cytotoxicity is associated with modulation of ERK signaling which may be partially mediated by regulation of phosphatase expression.

}, year = {2005}, journal = {Leukemia Research}, volume = {29}, pages = {1171-9}, month = {10/2005}, url = {http://www.sciencedirect.com/science/article/pii/S0145212605001475?via\%3Dihub}, language = {eng}, }