Loss of p53 expression correlates with metastatic phenotype and transcriptional profile in a new mouse model of head and neck cancer.
Mol Cancer Res
; 5(4): 351-62, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17426250
ABSTRACT
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most frequent cancer worldwide. Because HNSCC is largely acquired by environmental carcinogen exposure rather than through germ line mutations, there are no known familial forms of the disease in humans nor are there inbred rodent strains prone to spontaneous head and neck tumors. Transgenic animals with inactivation of tumor suppressor genes commonly mutated in human cases of HNSCC provide attractive models for studying the pathogenesis of head and neck cancer. p53 is the most frequently inactivated tumor suppressor gene in HNSCC. We used a chemical induction protocol in mice heterozygous for the p53 gene to evaluate how p53 inactivation contributed to head and neck carcinogenesis the mouse model. Metastatic squamous cell carcinomas developed in 100% of animals. Histopathologically, the tumors ranged from well to poorly differentiated and showed many molecular features of human HNSCC. Mice carrying only one p53 allele developed tumors with significantly reduced latency compared with wild-type controls (average, 18 versus 22 weeks). Metastatic cancer cells showed complete loss of p53 expression when compared with primary tumors. Transcriptional profiling showed not only distinct genetic differences between primary and metastatic tumors, but also when cancers from heterozygous null and wild-type animals were compared. Our results provide novel insights into the molecular genetics of tumor progression in head and neck cancer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
/
Regulação Neoplásica da Expressão Gênica
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Proteína Supressora de Tumor p53
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Análise de Sequência com Séries de Oligonucleotídeos
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Modelos Animais de Doenças
/
Neoplasias de Cabeça e Pescoço
Tipo de estudo:
Etiology_studies
/
Evaluation_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA