D J Leffell1. 1. Department of Dermatology, Section of Dermatologic Surgery and Cutaneous Oncology, and the Department of Surgery, Yale School of Medicine, CT, USA.
Abstract
BACKGROUND: Mutations in tumor suppressor gene p53 are very common in many human cancers. They are present in more than 90% of squamous cell carcinomas (SCCs) and are usually found in actinic keratoses (AKs). Data demonstrate a strong relationship between the early effects of ultraviolet radiation (UVR) on p53 in skin and the development of AK and SCC. OBJECTIVE: The purpose of this article is to review specific data about the p53 tumor suppressor gene, UVR, and their interaction to cause AKs. METHODS: The published, peer-reviewed literature is reviewed and a published proposal for the mechanism for UVR-induced carcinogenesis is explained. RESULTS: The specific effect of UVR on the p53 tumor suppressor gene, including its impact on apoptosis, in humans, and in animals, suggests a cause-effect relationship between UVR and the earliest mutations seen in AKs. CONCLUSION: AKs result from UVR in a process by which UVR mutates a known tumor suppressor gene (p53). It is likely that the mutated cells expand preferentially in a clonal fashion at the expense of the normal surrounding keratinocytes to develop into a clinical lesion of AK.
BACKGROUND: Mutations in tumor suppressor gene p53 are very common in many humancancers. They are present in more than 90% of squamous cell carcinomas (SCCs) and are usually found in actinic keratoses (AKs). Data demonstrate a strong relationship between the early effects of ultraviolet radiation (UVR) on p53 in skin and the development of AK and SCC. OBJECTIVE: The purpose of this article is to review specific data about the p53tumor suppressor gene, UVR, and their interaction to cause AKs. METHODS: The published, peer-reviewed literature is reviewed and a published proposal for the mechanism for UVR-induced carcinogenesis is explained. RESULTS: The specific effect of UVR on the p53tumor suppressor gene, including its impact on apoptosis, in humans, and in animals, suggests a cause-effect relationship between UVR and the earliest mutations seen in AKs. CONCLUSION: AKs result from UVR in a process by which UVR mutates a known tumor suppressor gene (p53). It is likely that the mutated cells expand preferentially in a clonal fashion at the expense of the normal surrounding keratinocytes to develop into a clinical lesion of AK.
Authors: Steffen Durinck; Christine Ho; Nicholas J Wang; Wilson Liao; Lakshmi R Jakkula; Eric A Collisson; Jennifer Pons; Sai-Wing Chan; Ernest T Lam; Catherine Chu; Kyunghee Park; Sung-woo Hong; Joe S Hur; Nam Huh; Isaac M Neuhaus; Siegrid S Yu; Roy C Grekin; Theodora M Mauro; James E Cleaver; Pui-Yan Kwok; Philip E LeBoit; Gad Getz; Kristian Cibulskis; Jon C Aster; Haiyan Huang; Elizabeth Purdom; Jian Li; Lars Bolund; Sarah T Arron; Joe W Gray; Paul T Spellman; Raymond J Cho Journal: Cancer Discov Date: 2011-06-29 Impact factor: 39.397
Authors: Michael P Underbrink; Heather L Howie; Kristin M Bedard; Jennifer I Koop; Denise A Galloway Journal: J Virol Date: 2008-08-20 Impact factor: 5.103