Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin Journal Article
| Authors: | Robanus-Maandag, E.; Giovannini, M.; Van Der Valk, M.; Niwa-Kawakita, M.; Abramowski, V.; Antonescu, C.; Thomas, G.; Berns, A. |
| Article Title: | Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin |
| Abstract: | Previously, we have mimicked human nenirofibromatosis type 2 (NF2) in conditional Nf2 mutant (P0Cre;Nf2flox2/flox2) mice. Schwannomas, characteristic for NF2, were found at low frequency in older mice. Here, we report that these mice, upon additional hemizygosity for p53, rapidly develop multiple tumours showing features consistent with malignant peripheral nerve sheath tumours. Thus, p53 hemizygosity promotes tumorigenesis of mutant Nf2 peripheral nerve cells. In contrast, young P0Cre;Nf2flox2/+;p53 +/- cis mice mainly succumb to Nf2/p53-related osteogenic tumours. Therefore, Cre-mediated early biallelic loss of Nf2 function in neural crest-derived cells hemizygons for p53 results in resistance to osteogenic tumours and increased susceptibility to peripheral nerve sheath tumours. |
| Keywords: | immunohistochemistry; bone tumor; gene mutation; promoter region; genetics; mutation; nonhuman; mouse; animal; animals; mice; allele; animal tissue; gene; neurofibromatosis; cancer susceptibility; animal experiment; animal model; genotype; carcinogenesis; animalia; cancer genetics; tumor suppressor gene; gene loss; malignant neoplastic disease; hemizygosity; neural crest; malignant transformation; mpnst; nerve sheath tumor; peripheral nerve tumor; osteoblast; nf2 gene; genes, p53; neurilemoma; neurilemmoma; genes, neurofibromatosis 2; male; female; priority journal; article; compensatory signalling; conditional knockout mice; p0 promoter |
| Journal Title: | Oncogene |
| Volume: | 23 |
| Issue: | 39 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2004-08-26 |
| Start Page: | 6541 |
| End Page: | 6547 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1207858 |
| PROVIDER: | scopus |
| PUBMED: | 15221010 |
| DOI/URL: | |
| Notes: | Oncogene -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: ONCNE -- Source: Scopus |
