The activity of extracellular signal-regulated kinase is required during G2/M phase before metaphase-anaphase transition in synchronized leukemia cell lines.

The pharmacological inhibitors of extracellular signal-regulated kinase (ERK) have been suggested as a novel molecular target-based therapy for acute myeloid leukemia. Several studies have established the role of ERK in cell cycle progression from G(1) to S phase in response to mitogen, but the role of ERK after the restriction point is less clarified. In this study, we used models of aphidicolin and nocodazole-synchronized HL-60 and NB4 leukemia cell lines to determine the kinetics of ERK activity during the progression of the cell cycle and to test the effects of commercially available inhibitors on G(2)/M progression of synchronized leukemia cells. In aphidicolin-synchronized cells, the activity of ERK was low during early S phase and increased at late S and G(2)/M phase of the cell cycle. The presence of MEK inhibitors PD 98059 and U0126 caused a delay in G(2)/M phase. In nocodazole-synchronized cells, the activity of ERK was low during M/G(1) transition and MEK inhibitors had no effects on return of the cells to G(1) phase. These results demonstrate that the activity of ERK is required during G(2)/M phase of leukemia cell cycle before the cells reach metaphase-anaphase transition.
AuthorsKatarina Matkovic, Vesna Lukinovic-Skudar, Hrvoje Banfic, Dora Visnjic
JournalInternational journal of hematology (Int J Hematol) Vol. 89 Issue 2 Pg. 159-66 (Mar 2009) ISSN: 1865-3774 [Electronic] United States
PMID19148588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aphidicolin
  • Extracellular Signal-Regulated MAP Kinases
  • Nocodazole
  • Anaphase
  • Aphidicolin (pharmacology)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Extracellular Signal-Regulated MAP Kinases (physiology)
  • G2 Phase
  • Humans
  • Leukemia (pathology)
  • Metaphase
  • Nocodazole (pharmacology)

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