Conflicts of interest JE and ES have received financial support for parts of their research from Heidelberg Pharma, Almirall, Shire and Natlmmune. JE has acted as a paid consultant to Roche Diagnostics. ES has acted as a paid consultant to Meda, Mavig, Almirall, Spirig, Heidelberg Pharma, Intendis. CU has acted as a paid consultant to Almirall and Spirig. PMR and ML have no conflict of interest.
UV-induced squamous cell carcinoma – a role for antiapoptotic signalling pathways
Article first published online: 22 SEP 2009
© 2009 The Authors. Journal Compilation © 2009 British Association of Dermatologists
British Journal of Dermatology
Special Issue: Advances in the Management of UVR induced Skin Cancers.
Volume 161, Issue Supplement s3, pages 107–115, November 2009
How to Cite
Rodust, P.M., Stockfleth, E., Ulrich, C., Leverkus, M. and Eberle, J. (2009), UV-induced squamous cell carcinoma – a role for antiapoptotic signalling pathways. British Journal of Dermatology, 161: 107–115. doi: 10.1111/j.1365-2133.2009.09458.x
- Issue published online: 22 SEP 2009
- Article first published online: 22 SEP 2009
- Accepted for publication 7 August 2009
- actinic keratosis;
- Bcl-2 proteins;
- death ligands;
- EGF receptor;
The incidence of nonmelanoma skin cancer including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) has dramatically increased in the last decades, and chronic sun exposure was identified as a main etiologic agent. UV radiation may produce DNA damage either directly or through reactive oxygen species (ROS). As mutations caused by UV may lead to skin cancer due to oncogene activation and tumor suppressor gene inactivation, efficient safeguard mechanisms have been developed during evolution. These enclose induction of apoptosis and formation sunburn cells aiming at the removal of premalignant cells. The keratinocyte apoptotic machinery in response to UV consists of both intrinsic/mitochondrial and extrinsic/death receptor-mediated cell-death pathways, which are particularly regulated by mitogen-activated protein kinases (MAPKs, JNK and p38) and the tumor-suppressor protein p53. For development of skin cancer, it appears that critical steps in apoptosis control are dysregulated leading to resistance both to death ligand-mediated and intrinsic proapoptotic pathways. These particularly include inactivation of p53, as well as activation of EGFR, COX-2 and MAPKs, which result in specific regulation of Bcl-2 proteins, death ligands and death receptors. The final unravelling of apoptosis regulation in epithelial skin cancer may allow the development of new targeted therapeutic strategies.