[Frontiers in Bioscience 11, 3003 -3013, September 1, 2006]

Recent advances in melanoma research

Jon A. Reed 1,2, and Estela E. Medrano 2,3,4

1 Department of Pathology, 2 Department of Dermatology, 3 Huffington Center on Aging, 4 Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The Mitogen-Activated Protein Kinase (MAPK) / Extracellular Signal-Regulated Kinase (ERK) Pathway: upstream determinants of normal cell behavior are aberrant in malignant melanoma
3.1. Oncogenic Ras: recruitment of the MAPK/ERK cascade and a potential target for constitutive pathway activation
3.2. RAF kinases: a target for pathway activation responsible for carrying the signal downstream
3.3. B-RAFV600E triggering cellular senescence in nevi
3.4. MEK and ERK: kinases that transmit signals to the nucleus, and mediate cross talk with other signaling pathways
3.5. Oncogenic signaling through erbB family receptors: another way of activating the MAPK/ERK pathway in melanomas?
4. The many lives of MITF: a master pigment regulator, a growth inhibitory/pro-apoptotic protein, a survival oncogenes, or all of the above?
5. More than just p16INK4a: the (very) aberrant melanoma cell cycle
5.1. The oncogenic activity of the low molecular weight forms of cyclin E
5.2. CDK2: required for melanoma proliferation
6. Epigenetics and melanoma
7. General conclusions
8. Acknowledgments
9. References

1. ABSTRACT

At the end of the last decade, sporadic melanomas were still considered a genetic black box. Fortunately, in the last few years the box has been opened bringing to light melanoma-relevant oncogenes, aberrant signal transduction pathways, critical alterations in the melanoma cell cycle that go beyond p16INK4a, and melanoma- microenvironment interactions that are essential for tumor progression. This review will discuss some of the latest findings in melanoma research including the critical role of the MAPK pathway in the genesis of melanoma and senescence of nevi, the paradoxical tumor suppressor and oncogenic activities of the transcription factor MITF, and the unexpected oncogenic activities of the low molecular weight forms of cyclin E.