Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2003 Nov;163(5):1729-33.

p53 haploinsufficiency profoundly accelerates the onset of tongue tumors in mice lacking the xeroderma pigmentosum group A gene.

Author information

1
Department of Oral Pathology, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan. idef@dent.meikai.ac.jp

Abstract

Mice lacking the xeroderma pigmentosum group A gene (XPA-/- mice), which have a complete deficiency in nucleotide excision repair (NER), are highly predisposed to tongue squamous cell carcinoma (SCC) when exposed to 4-nitroquinoline 1-oxide (4NQO). To explore the effects of the interaction of the NER machinery with p53 in oral tumorigenesis, we generated an XPA-/- mouse strain carrying mutant alleles for p53. This mouse model of 4NQO carcinogenesis demonstrated that despite the same tumor frequency, XPA-/-p53+/- mice reached 100% SCC incidence at 25 weeks compared with 50 weeks for XPA-/-p53+/+ littermates. XPA-/-p53-/- mice succumbed to spontaneous thymic lymphomas before the development of tongue tumors (before 13 weeks of age). SCC originated in XPA-/-p53+/- mice maintained the p53+/- genotype and the retained wild-type p53 allele appeared to be structurally intact. Only one of 20 XPA-/-p53+/+ SCC showed a missense mutation of p53. Collectively, the accelerated tongue tumor growth may be a consequence of haploinsufficiency but not of mutation of p53 in the context of NER deficiency.

PMID:
14578172
PMCID:
PMC1892426
DOI:
10.1016/S0002-9440(10)63531-6
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center