p53 protein expression in benign and malignant skin tumours

Cooper, P.; Lee, J.A.; Quinn, Anthony G.; Harrison, David J.; Lane, David P.; Hornh, C.H.W.; Rees, Jonathan; Angus, Brian

doi:10.1111/j.1365-2133.1993.tb00164.x

Cited by 98 publications

(46 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in concordance with the increased expression of p53 seen in DMBA/TPA-or UV-induced mouse skin tumors and in human SCCs (McGregor et al, 1992;Mitsunaga et al, 1995;Ren et al, 1996b;Ro et al, 1993;Tong et al, 1997). This increase is considered to be a response to DNA damage or mutations in the p53 gene.…”

Section: High Proliferation Rate In Transgenic Skin and Tumorssupporting

confidence: 68%

Inhibition of Rel/Nuclear Factor-κB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development

Hogerlinden

Auer²,

Toftgárd

2002

Oncogene

View full text Add to dashboard Cite

In recent years a growth inhibitory role in skin for the Rel/NF-kB transcription factors has been established, and the block of Rel/NF-kB signaling results in rapid development of spontaneous skin cancer. The molecular mechanism underlying tumor development is however unknown. In the present study, we show that inhibition of NF-kB signaling in mouse skin by targeted expression of degradation resistant IkB-a generates transgenic keratinocytes unable to arrest the cell cycle in response to DNA damage induced by g-radiation. The results indicate that transgenic keratinocytes have a defect at the G1-S checkpoint whereas the G2-M checkpoint response was found to be intact. However, transgenic keratinocytes still respond by induction of the cyclin dependent kinase inhibitor p21 Cip1/Waf after exposure to g-radiation. In the spontaneous skin tumors that develop in transgenic mice no mutations were found in the Haras or p53 gene, suggesting that inhibition of NF-kB signaling in skin can induce cancer development independently of initiating mutations in the Ha-ras gene or additional mutations in the p53 gene. These findings demonstrate an involvement of NF-kB signaling in the DNA damage response and cell cycle checkpoint control in the skin.

show abstract

Section: High Proliferation Rate In Transgenic Skin and Tumorssupporting

confidence: 68%

Inhibition of Rel/Nuclear Factor-κB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development

Hogerlinden

Auer²,

Toftgárd

2002

Oncogene

View full text Add to dashboard Cite

show abstract

“…In our study, p53 immunopositivity was observed in 68% of the samples, which is a clearly higher p53 expression level compared with the studies in which the same antibody without antigen retrieval was used (Lassam et al, 1993;Ro et al, 1993). In contrast, the fraction of immunopositivity in our material was very low, only about 20% of the tumours showing p53 signal in more than 5% of the tumour cell nuclei.…”

Section: Discussioncontrasting

confidence: 51%

p21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

et al. 1999

Br J Cancer

View full text Add to dashboard Cite

Tumour suppressor p21 WAF1/CIP1 is the main downstream effector gene mediating p53-induced cell cycle arrest, up-regulated by normal wild-type p53 (El-Deiry et al, 1993). In addition to direct transcriptional induction by the tumour suppressor p53, various other signals can induce p21 expression in the absence of wildtype p53 (Michieli et al, 1994;Zeng and El-Deiry, 1996). Harper et al (1993) showed that the ability of the p21 gene product to arrest the cell cycle is based on its virtue to bind and inhibit active cyclin/CDK complexes needed in DNA replication and cell cycle progression. p21 can also inhibit DNA replication by directly binding to the proliferating cell nuclear antigen (PCNA) molecule, thus inhibiting the ability of DNA polymerase δ to extend new DNA chains but still allowing the DNA repair function to continue (Flores-Rozas et al, 1994;Waga et al, 1994;Podust et al, 1995).In human melanoma cell lines, induction of p21 is independent of wild-type p53 expression (Jiang et al, 1995;Vidal et al, 1995), and elevated expression of p21 is associated with melanoma differentiation, growth arrest and metastatic suppression (Jiang et al, 1995). However, the knowledge of p21 expression in clinical materials of cutaneous malignant melanoma is rather limited. Maelandsmo et al (1996) revealed a significant correlation between elevated p21 expression and increasing tumour thickness in superficially spreading melanoma, but no correlation between p21 and survival was found. Elsewhere, a significant overexpression of p21 has been demonstrated in primary and metastatic melanomas (Trotter et al, 1997).As far as the authors are aware, no previous study has compared the relationships between p21, p53 and PCNA expression in primary stage I cutaneous melanoma. In the present study, we used immunohistochemistry to analyse the above-mentioned relationships in a cohort of 369 patients with long-term follow-up data. In addition, our aim was to analyse whether p21 protein levels are related to clinical data, histological parameters (Clark and Breslow levels) and prognosis. MATERIALS AND METHODS PatientsThe retrospective study consists of a consecutive series of 369 clinical stage I cutaneous malignant melanoma patients with complete clinical and histopathological data available, who were diagnosed and treated in the district of Kuopio University Hospital, Finland, between 1974 and 1989. The clinical staging of all tumours was carried out according to UICC (UICC, 1987). Because of insufficient tumour material, pigment or technical artefacts, there were 267 valid immunostainings for p21, 284 for p53 and 219 for PCNA respectively. Patient records were reviewed and the pertinent clinical and histopathological data of the patients are shown in Table 1. The mean follow-up time of all 369 patients was 6.4 years (range 0.2-18 years). When the analysis was restricted to patients with p21, p53 or PCNA data, the mean follow-up times were 6.3 years (range 0.5-18 years), 6.3 years (range 0.5-18 years) or 7.2 years (range 0.5-18 years) re...

show abstract

“…Ro et al observed p53 positivity in 42% of basal cell carcinomas. 12 They concluded that detectable p53 protein is a common occurrence in malignant epithelial lesions, but it does not correlate with the malignant phenotype or with metastatic potential. In our study , the distribution of positivity of p53 protein in each of the three groups was: 4,7% of BSCC, 19,1% of IBCC, 19,1% of NIBCC.…”

Section: Discussionmentioning

confidence: 99%

Value of p53 protein in biological behavior of basal cell carcinoma and in normal epithelia adjacent to carcinomas

Demirkan

Çolakoğlu

Düzcan

2000

Pathol. Oncol. Res.

View full text Add to dashboard Cite

p53 protein expression in benign and malignant skin tumours

Cited by 98 publications

References 10 publications

Inhibition of Rel/Nuclear Factor-κB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development

Inhibition of Rel/Nuclear Factor-κB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development

p21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

Value of p53 protein in biological behavior of basal cell carcinoma and in normal epithelia adjacent to carcinomas

Contact Info

Product

Resources

About