Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo

[EN]Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here t...

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Detalles Bibliográficos
Autores: Díaz Rodríguez, María Elena, Sotillo, Rocio, Schvartzman, Juan-Manuel, Benezra, Robert
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/167952
Acceso en línea:http://hdl.handle.net/10366/167952
Access Level:acceso abierto
Palabra clave:Aneuploidy
Cancer
Chromosome instability
Kinetochores
Mitosis
Chromosomal Instability
Doxycycline
Microtubule-Associated Proteins
Gene Expression Regulation
Neoplasms
Nuclear Proteins
Tissue Distribution
Animals
Cell Cycle Proteins
Mice
2302 Bioquímica
inestabilidad cromosómica
proteínas asociadas a microtúbulos
neoplasias
mitosis
ratones
proteínas nucleares
aneuploidía
cinetocoros
regulación de la expresión génica
animales
distribución tisular
doxiciclina
proteínas del ciclo celular
Descripción
Sumario:[EN]Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here that the overexpression of Hec1 in an inducible mouse model results in mitotic checkpoint hyperactivation. As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy. These results underscore the role of chromosomal instability as a result of mitotic checkpoint hyperactivation in the initiation of tumorigenesis.