Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment.

ERK1/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis.

Mirmohammadsadegh A, Mota R, Gustrau A, Hassan M, Nambiar S, Marini A, Bojar H, Tannapfel A, Hengge UR

Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.

Activation (phosphorylation) of mitogen-activated protein kinase (MAPK) signal transduction through BRAF and RAS causes a variety of functional effects including cell survival and cell death. In this study, we observed high extracellular signal-regulated kinase (ERK)1/2 phosphorylation levels in clinical melanoma metastases and various melanoma cell lines. Treatment of melanoma cell lines with cisplatin, a potent antitumor agent, increased the level of phosphorylated-ERK (P-ERK)1/2 and enhanced chemoresistance through activation of the cell survival protein 90-kDa ribosomal S6 kinase (RSK)1. The mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) was able to block this effect and reduced cell viability and sensitized cells to cisplatin-induced apoptosis, as shown by PARP cleavage, caspase 3 expression, and annexin-V staining. In conclusion, the MAP kinase-ERK pathway is activated in melanoma and reduces the sensitivity of melanoma to cisplatin. Thus, inhibition of ERK1/2 in combination with selected chemotherapeutic agents may hold promise for more effective therapy of melanoma.

Published 16 August 2007 in J Invest Dermatol, 127(9): 2207-15.
Full-text of this article is available online (may require subscription).

© 2004-2008 Melanoma Research Today. All Rights Reserved.