Loss of mitotic spindle checkpoint activity predisposes to chromosomal instability at early stages of fibrosarcoma development.
Cell Cycle
; 2(3): 238-45, 2003.
Article
em En
| MEDLINE
| ID: mdl-12734433
ABSTRACT
Mice carrying the bovine papillomavirus type I genome develop dermal fibrosarcomas in a multiple step process characterized by distinctive proliferative stages. Chromosomal aberrations are identified early in this tumorigenic pathway, however, the mechanism that originates them is unknown. Using a functional assay, we investigated the status of the mitotic spindle cell cycle checkpoint (MSCCC) that regulates the metaphase to anaphase transition, in cells representing different stages of fibrosarcoma progression. Loss of MSCCC activity was apparent in mild fibromatosis and completely abolished in aggressive fibromatosis and fibrosarcoma lesions. This altered MSCCC status was confirmed biochemically by deregulated expression of Cks1 protein and unscheduled cyclin B metabolism. Immunoprecipitation and sequencing analyses indicated that mutation of p53 was not required for the abrogation of the MSCCC. These results demonstrate that loss of mitotic spindle checkpoint activity predisposes to chromosomal instability at early stages of fibrosarcoma development. To our knowledge, these studies constitute the first report of a transition in MSCCC activity in a tumorigenesis model.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Aberrações Cromossômicas
/
Genes cdc
/
Predisposição Genética para Doença
/
Fibrossarcoma
/
Mitose
/
Fuso Acromático
/
Mutação
Limite:
Animals
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Reino Unido