Sunburn and p53 in the onset of skin cancer

Annemarie Ziegler; Alan S. Jonason; David J. Leffellt; Jeffrey A. Simon; Harsh W. Sharma; Jonathan Kimmelman; Lee Remington; Tyler Jacks; Douglas E. Brash

doi:10.1038/372773a0

Sunburn and p53 in the onset of skin cancer

Annemarie Ziegler, Alan S. Jonason, David J. Leffellt, Jeffrey A. Simon, Harsh W. Sharma, Jonathan Kimmelman, Lee Remington, Tyler Jacks, Douglas E. Brash

Genetics, Cell Biology and Development (CBS)

Research output: Contribution to journal › Article › peer-review

1398 Scopus citations

Abstract

SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis^1-3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs^4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells⁶, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the- tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.

Original language	English (US)
Pages (from-to)	773-776
Number of pages	4
Journal	Nature
Volume	372
Issue number	6508
DOIs	https://doi.org/10.1038/372773a0
State	Published - Jan 1 1994

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title = "Sunburn and p53 in the onset of skin cancer",

abstract = "SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis1-3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells6, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the- tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.",

author = "Annemarie Ziegler and Jonason, {Alan S.} and Leffellt, {David J.} and Simon, {Jeffrey A.} and Sharma, {Harsh W.} and Jonathan Kimmelman and Lee Remington and Tyler Jacks and Brash, {Douglas E.}",

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T1 - Sunburn and p53 in the onset of skin cancer

AU - Ziegler, Annemarie

AU - Jonason, Alan S.

AU - Leffellt, David J.

AU - Simon, Jeffrey A.

AU - Sharma, Harsh W.

AU - Kimmelman, Jonathan

AU - Remington, Lee

AU - Jacks, Tyler

AU - Brash, Douglas E.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis1-3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells6, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the- tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.

AB - SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis1-3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells6, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the- tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.

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Sunburn and p53 in the onset of skin cancer

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