Back to Search
Start Over
Alpha-melanocyte stimulating hormone potentiates p16/CDKN2A expression in human skin after ultraviolet irradiation.
- Source :
-
Cancer research [Cancer Res] 2002 Feb 01; Vol. 62 (3), pp. 875-80. - Publication Year :
- 2002
-
Abstract
- The contribution of the UV component of sunlight to the development of skin cancer is widely acknowledged, although the molecular mechanisms that are disrupted by UV radiation (UVR) resulting in the loss of normal growth controls of the epidermal stem cell keratinocytes and melanocytes is still poorly understood. Alpha-melanocyte stimulating hormone (alpha-MSH), acting via its receptor MC1, has a key role in skin pigmentation and the melanizing response after exposure to UVR. The cell cycle inhibitor p16/CDKN2A also appears to have an important function in a cell cycle checkpoint response in skin after exposure to UVR. Both of these genes have been identified as risk factors in skin cancer, MC1R variants are associated with increased risk to both melanoma and nonmelanoma skin cancers, and p16/CDKN2A with increased risk of melanoma. Here we demonstrate that the increased expression of p16 after exposure to suberythemal doses of UVR is potentiated by alpha-MSH, a ligand for MC1R, and this effect is mimicked by cAMP, the intracellular mediator of alpha-MSH signaling via the MC1 receptor. This link between p16 and MC1R may provide a molecular basis for the increased skin cancer risk associated with MC1R polymorphisms.
- Subjects :
- Humans
Keratinocytes drug effects
Keratinocytes metabolism
Keratinocytes radiation effects
Melanocytes drug effects
Melanocytes metabolism
Melanocytes radiation effects
Organ Culture Techniques
Receptors, Corticotropin physiology
Receptors, Melanocortin
Signal Transduction
Skin drug effects
Cyclin-Dependent Kinase Inhibitor p16 biosynthesis
Skin metabolism
Skin radiation effects
Ultraviolet Rays
alpha-MSH analogs & derivatives
alpha-MSH pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 62
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 11830546