12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase expression and AML cell survival

Dale G. Schaar, Hao Liu, Shashi Sharma, Yi Ting, John Martin, Curtis Krier, Marie Ciardella, Mona Osman, Lauri Goodell, Daniel A. Notterman, Roger K. Strair

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1171-1179
Number of pages9
JournalLeukemia Research
Volume29
Issue number10
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Keywords

  • 12-O-Tetradecanoylphorbol-13-acetate
  • Acute myelogenous leukemia
  • Apoptosis
  • Differentiation
  • Gene expression
  • MAPK dual-specificity phosphatases (DUSP)
  • Mitogen-activated protein kinase (MAPK)

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  • Cite this

    Schaar, D. G., Liu, H., Sharma, S., Ting, Y., Martin, J., Krier, C., Ciardella, M., Osman, M., Goodell, L., Notterman, D. A., & Strair, R. K. (2005). 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase expression and AML cell survival. Leukemia Research, 29(10), 1171-1179. https://doi.org/10.1016/j.leukres.2005.02.019