Transforming growth factor-beta pathway serves as a primary tumor suppressor in CD8+ T cell tumorigenesis.
Cancer Res
; 64(18): 6524-9, 2004 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-15374963
ABSTRACT
Tumorigenesis in rodents, as well as in humans, has been shown to be a multistep process, with each step reflecting an altered gene product or gene regulatory process leading to autonomy of cell growth. Initial genetic mutations are often associated with dysfunctional growth regulation, as is demonstrated in several transgenic mouse models. These changes are often followed by alterations in tumor suppressor gene function, allowing unchecked cell cycle progression and, by genomic instability, additional genetic mutations responsible for tumor metastasis. Here we show that reduced transforming growth factor-beta signaling in T lymphocytes leads to a rapid expansion of a CD8+ memory T-cell population and a subsequent transformation to leukemia/lymphoma as shown by multiple criteria, including peripheral blood cell counts histology, T-cell receptor monoclonality, and host transferability. Furthermore, spectral karyotype analysis of the tumors shows that the tumors have various chromosomal aberrations. These results suggest that reduced transforming growth factor-beta signaling acts as a primary carcinogenic event, allowing uncontrolled proliferation with consequent accumulation of genetic defects and leukemic transformation.
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Banco de datos:
MEDLINE
Asunto principal:
Leucemia de Células T
/
Factor de Crecimiento Transformador beta
/
Linfocitos T CD8-positivos
/
Trastornos Linfoproliferativos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Res
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos