Tumor Suppressor Gene Mutations and Photocarcinogenesis

Ziegler, Annemarie; Jonason, Alan S.; Simon, John; Leffell, David J.; Brash, Douglas E.

doi:10.1111/j.1751-1097.1996.tb03064.x

Cited by 52 publications

(39 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both activation of cellular signaling pathways and DNA damage can change the phosphorylation levels of p53 protein resulting in cell cycle arrest and apoptosis. The most common DNA damage is forming cyclobutane pyrimidine dimmers (CPD) mutations that stimulate increases in p53 phosphorylation levels through activating chks (van Kranen et al, 1995;Ziegler et al, 1996). In addition, Chk activation induced by DNA damage, caused by ionizing radiation (IR), reactive oxygen species (ROS), and UV irradiation, increases p53 phosphorylation levels at various sites and is mediated by activation of Polo-like kinase (PLK), (Xie et al, 2001a(Xie et al, , b, 2002.…”

Section: Introductionmentioning

confidence: 99%

Ultraviolet irradiation-induced K+ channel activity involving p53 activation in corneal epithelial cells

Dai

2005

Oncogene

View full text Add to dashboard Cite

Recent studies from our lab found that ultraviolet (UV) irradiation induces a voltage-gated potassium (Kv) channel activation and subsequently activates JNK signaling pathway resulting in apoptosis. The present study in rabbit corneal epithelial (RCE) cells is to investigate mechanisms of UV irradiation-induced Kv channel activity involving p53 activation in parallel to DNA damage-induced signaling pathway. UV irradiationinduced signaling events were characterized by measurements of JNK activation and further downstream p53 phosphorylation. UV irradiation elicited an early response in the cell membrane through activation of Kv channels to activate the JNK signaling pathway and p53 phosphorylation. Exposure of RCE cells to UV irradiation within a few min resulted in JNK and p53 activations that were markedly inhibited by suppression of Kv channel activity. However, suppression of Kv channel activity failed to prevent p53 activation induced by extended DNA damages through prolonging UV exposure time (more than 15 min). In addition, caffeine inhibited UV-induced activation of SEK, an upstream MAPK kinase of JNK, resulting in suppression of both Kv channel-involved and DNA damage-induced p53 activation. Our results indicate in these cells that UV irradiation induces earlier and later intracellular events that link to activation of JNK and p53. The early event in response to UV irradiation is initiated by activating Kv channels in the cell membrane, and the later event is predominated by UV irradiationcaused DNA damage.

show abstract

Section: Introductionmentioning

confidence: 99%

Ultraviolet irradiation-induced K+ channel activity involving p53 activation in corneal epithelial cells

Dai

2005

Oncogene

View full text Add to dashboard Cite

show abstract

“…Mutation of the p53 gene is one frequent, known genetic alteration found in SCC and BCC. 3 In addition, activation of the sonic hedgehog/patched signaling pathway seems essential for development of BCC. 4,5 In human skin there exists a multitude of p53-immunoreactive clusters of morphologically normal epidermal keratinocytes.…”

mentioning

confidence: 99%

Persistent p53 Mutations in Single Cells from Normal Human Skin

Gao

Persson

Berne

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

Epidermal clones of p53-mutated keratinocytes are abundant in chronically sun-exposed skin and may play an important role in early development of skin cancer. Advanced laser capture microdissection enables genetic analysis of targeted cells from tissue sections without contamination from neighboring cells. In this study p53 gene mutations were characterized in single cells from normal, chronically sunexposed skin. Biopsies were obtained from skin subjected to daily summer sun and skin totally protected from the sun by blue denim fabric. Using laser capture microdissection, 172 single-cell samples were retrieved from four biopsies and analyzed using single-cell polymerase chain reaction and direct DNA sequencing. A total of 14 different mutations were identified in 26 of 99 keratinocytes from which the p53 gene could be amplified. Mutations displayed a typical UV signature and were detected in both scattered keratinocytes and in a small cluster of p53-immunoreactive keratinocytes. This minute epidermal p53 clone had a diameter of 10 to 15 basal cells. Two missense mutations were found in all layers of epidermis within the p53 clone. The presented data show that p53 mutations are common in normal skin and that a clone of keratinocytes with a mutated p53 gene prevailed despite 2 months of total protection from ultraviolet light. 1 Ultraviolet (UV) radiation from the sun is accepted as a major risk factor and tumor cells exhibit mutations with typical UV signature in cancerrelated genes.2 Skin carcinogenesis is a multistep process, in which the early clandestine events, preceding malignant transformation are primarily unknown. In chronically sun-damaged skin SCC develops through stages of actinic keratosis and SCC in situ, whereas no such precursor lesions are known for BCC. Although several genes and pathways are important for development of skin cancer, the genetic events underlying the different steps from a normal cell to SCC or BCC are virtually unknown. Mutation of the p53 gene is one frequent, known genetic alteration found in SCC and BCC. In addition, activation of the sonic hedgehog/patched signaling pathway seems essential for development of BCC. 4,5 In human skin there exists a multitude of p53-immunoreactive clusters of morphologically normal epidermal keratinocytes.6 -8 These p53 clones are predominantly found in chronically sun-exposed skin. Microdissection followed by polymerase chain reaction (PCR) and direct DNA sequencing has shown an underlying p53 mutation in at least 70% of analyzed cases. Epidermal p53 clones and adjacent cancers have never been shown to share the same p53 mutation and thus there is no solid evidence of a genetic link between p53 clones and any specific type of skin cancer.9,10 However, the incidence and location of p53 clones suggest a role for p53 mutations in skin cancer. Mutations in the p53 gene have also been detected in UV-irradiated mouse skin months before the gross appearance of skin tumors, suggesting that p53 mutations are an early event for the development of skin ...

show abstract

“…The apoptotic response of cells within the epidermis is in part dependent on the p53 tumour suppressor protein Ziegler et al, 1996), however other p53-independent mechanisms have also been identified (Gniadecki et al, 1997). Whilst the role of p53 in protecting the epidermis from UV-induced skin carcinomas is clearly established in murine models (Donehower et al, 1992;Ananthaswamy et al, 1997;Jiang et al, 1999), there is conflicting evidence as to the protective role of p53 in adult human skin.…”

mentioning

confidence: 99%

Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus

et al. 2002

View full text Add to dashboard Cite

We have investigated the apoptotic levels and expression of the apoptotic inducer Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human papillomavirus status from immunocompetent patients were analysed for the expression of the Bak protein, and the expression profile was compared both to the presence of apoptotic cells and the proliferation marker Ki-67. We demonstrate an inverse correlation between human papillomavirus positivity and Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic cells being detected in the human papillomavirus positive tumours. Bak expression was not observed in basal cell carcinomas irrespective of human papillomavirus status, suggesting that Bak only plays a role in signalling apoptosis in squamous, but not basal, cell cancers. No differences were observed in the proliferation rates between papillomavirus positive and negative squamous cell tumours. However, a significant decrease in the number of apoptotic cells was observed in human papillomavirus-positive squamous cell carcinomas which suggests that the virus may have significantly altered the relationship between proliferation and apoptosis in a proportion of these tumours.

show abstract

Tumor Suppressor Gene Mutations and Photocarcinogenesis

Cited by 52 publications

References 23 publications

Ultraviolet irradiation-induced K+ channel activity involving p53 activation in corneal epithelial cells

Ultraviolet irradiation-induced K+ channel activity involving p53 activation in corneal epithelial cells

Persistent p53 Mutations in Single Cells from Normal Human Skin

Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus

Contact Info

Product

Resources

About