Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

Veldhoen, Nik; Stewart, Janet; Brown, Robert E.; Milner, Jo

doi:10.1038/sj.onc.1201489

Cited by 57 publications

(51 citation statements)

References 28 publications

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“…Recently similar mutations within the canine p53 gene have been identi®ed in a small number of canine cancer types including: thyroid carcinoma (Devilee et al, 1994), oral papilloma (Mayr et al, 1994), mammary tumours (Van Leeuwen et al, 1996), osteosarcoma (Van Leeuwen et al, 1997), circumanal gland adenoma (Mayr et al, 1997) and lymphoma (Veldhoen et al, 1998). Overexpression of the canine p53 protein was also observed in tumours of epithelial, mesenchymal and round cell origins (Sagartz et al, 1996;Gamblin et al, 1997;Wolf et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein

Veldhoen

Milner

1998

Oncogene

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The p53 tumour suppressor protein plays a central role in the maintenance of genomic integrity. Mutations of the p53 gene are found in a number of canine cancers and many contribute to tumour formation. Here we describe isolation and expression of the complete wild type canine p53 cDNA. The encoded full length canine p53 protein displays strong sequence homology with p53 proteins from other higher vertebrates. Canine p53 protein produced in vitro was shown to recognize and bind to p53-speci®c DNA targets derived from the p21 and GADD45 promoters and to a consensus p53 binding site. We also show that canine p53 associates with oligonucleotides representing damaged DNA sites and undergoes proteolytic cleavage similar to that described for murine and human p53 proteins. Finally, we show that the canine p53 protein is able to transcriptionally activate a p53-dependent reporter gene in vivo. The results suggest that canine p53 is similar both in structure and function to human p53 and that canine cancer may provide a useful clinical model in the search for e ective anti-cancer therapies based on p53.

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Section: Introductionmentioning

confidence: 99%

Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein

Veldhoen

Milner

1998

Oncogene

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“…Starting with vertebrates, more than 25 p53 genes or cDNAs were isolated and sequenced, providing a basis for developing new animal models to study this gene (Soussi and May, 1996). Indeed, in the case of the cat, cattle and dog, mutations in the p53 gene have been detected in the central region where mutational hot spots for human cancer are located (Dequiedt et al, 1995;Mayr et al, 2000;Veldhoen et al, 1998). Even more interesting is the identi®cation of the p53 gene in Drosophila (Brodsky et al, 2000;Jin et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line

2001

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In mammalian cells, the p53 protein is a key regulator of the cell cycle following DNA damage. In the present study, we investigated the function of p53 in the A6 amphibian cell line. Using various speci®c Xenopus p53 monoclonal antibodies, we showed that Xenopus p53 accumulates after DNA damage, including gamma and UV irradiation or treatment with adriamycin. Such accumulation is accompanied by an increase in the apparent molecular weight of the protein. This change was shown to be the result of a phosphorylation event that occurs after DNA damage. Accumulation of Xenopus p53 is parallel to a drastic change in the cell cycle distribution. Brief exposure to adriamycin or gamma irradiation induces reversible growth arrest, whereas long-term exposure to adriamycin leads to apoptosis. Taken together, these results indicate that p53 has a similar behaviour in frog cells and mammalian cells, and that it conserves two activities, cell cycle arrest and apoptosis. Oncogene (2001) 20, 3766 ± 3775.

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“…By these regulations, p53 selects target promoters of several genes by changing its structure and affinity to bind to the DNA sequences. Mutations in the p53 genes are the commonest alteration in human and animal cancers [18,25,34,38]. These mutations in the evolutionarily conserved codons, called "hot spot", are common in diverse types of mammalian cancers, and some mutants lose transcriptional activation potency, and their ability to bind to DNA [19,20,30].…”

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confidence: 99%

The Presence of a Short Form of p53 in Chicken Lymphoblastoid Cell Lines during Apoptosis

Takagi

Takeda

Asada

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. To examine the roles of a short form of p53 in the regulation of apoptosis in chicken lymphoblastoid tumor cell lines derived from Marek's disease (MD) and avian leukosis (AL), the expressions of the p53 proteins were analyzed in these cell lines in which apoptosis was chemically induced. In MSB1-O derived from MD, the expression of a 40 kDa protein of p53 was decreased and that of a 32 kDa protein, a short form of p53, was increased during apoptosis induced by actinomycin D. In 1104B1 derived from AL, the expressions of 42 and 32 kDa of p53 were increased during the apoptosis. The short form of p53 was undetectable in these cell lines when apoptosis was blocked by the pretreatment with endonuclease inhibitor, Zn 2+ , protease inhibitors, TPCK and TLCK, or caspase inhibitor, Z-VAD-FMK. In the transcriptional level, the expressions of bcl-2 and IAP were decreased in these cell lines during actinomycin Dinduced apoptosis, but no change was detected in the expression level of p53. These results suggest that, in these chicken tumors, the short form of p53 could play a role in the initiation of apoptosis induced by the chemotherapeutic compound, and that the regulation of its expression may be important for the maintenance of transformation status. KEY WORDS: apoptosis, Marek's disease, p53.

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Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

Cited by 57 publications

References 28 publications

Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein

Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein

Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line

The Presence of a Short Form of p53 in Chicken Lymphoblastoid Cell Lines during Apoptosis

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