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.
Matkovic
Katarina
K
Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia.
Lukinovic-Skudar
Vesna
V
Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia.
Banfic
Hrvoje
H
Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia.
Visnjic
Dora
D
Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia. visnjic@mef.hr.|Zavod za fiziologiju, Medicinski fakultet, Sveuciliste u Zagrebu, Salata 3, PO Box 978, 10 001, Zagreb, Croatia. visnjic@mef.hr.
D000705:Anaphase; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D016195:G2 Phase; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008677:Metaphase; D015739:Nocodazole / Q000494:pharmacology
D016590:Aphidicolin; D048049:Extracellular Signal-Regulated MAP Kinases; D015739:Nocodazole