Mitogen-activated protein kinases control p 27 / Kip 1 expression and growth of human melanoma cells

The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase (ERK)1 and ERK2, involved in regulating cell growth and differentiation, are constitutively active in A375 and WM239 human melanoma cells. Using PD098059, an inhibitor of MAPK kinase (MEK), we investigated the role of persistently activated ERK1}2 in cell growth. The inhibition of MAPK activity induced a dose-dependent growth arrest in G ! }G " phase. Correspondingly, we observed the upregulation of the cyclin-dependent kinase (Cdk) inhibitor p27} Kip1 and hypophosphorylation of the retinoblastoma protein.

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