[Frontiers in Bioscience S2, 11-17, January 1, 2010]

The shady side of sunlight: current understanding of the mechanisms underlying UV-induction of skin cancers

Alison Trappey1, Augusta Fernando1, Rajiv Gaur1, Madhwa Raj2, Allal Ouhtit1

1Department of Pthology, Louisiana State University Health Sciences Center, New Orleans, LA, 2Department of Obstetrics-Gynecology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Skin
2.2. Sunlight ultraviolet radiation
2.3. DNA damage
2.4. Non-melanoma skin cancer
2.5. Melanoma
3. Molecular mechanisms of UV-induced non-melanoma skin cancers
3.1. The p53 pathway
3.2. Deregulation of Apoptosis by UV
3.3. Other genes
4. Molecular mechanisms of UV-induced melanoma
4.1. UV and P16/Rb
4.2. UV and P53/Rb
5. Conclusion
6. Acknowledgements
7. References

1. ABSTRACT

The incidence of skin cancer has been rising at an astonishing rate, particularly that of the deadliest skin cancer, melanoma. While the molecular mechanisms of sunlight ultraviolet radiation (UV)-induced non-melanoma skin cancer (NMSC) have been well documented, there is a major gap in our current knowledge of how UV initiates melanoma. However, the components of the retinoblastoma (Rb) pathway, the p53 and the p16 pathways are considered the major targets of UV-induced NMSC and melanoma, respectively. Our recent study has revealed that these two pathways coordinate the early responses to UV radiation in the skin. Here, we review the value of studies targeting these early events of skin carcinogenesis, with specific focus on the critical role of the components of the Rb pathway.