K-ras proto-oncogene exhibits tumor suppressor activity as its absence promotes tumorigenesis in murine teratomas.
Mol Cancer Res
; 1(11): 820-5, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-14517344
ABSTRACT
Ras proteins transduce signals from membrane-bound receptors via multiple downstream effector pathways and thereby affect fundamental cellular processes, including proliferation, apoptosis, and differentiation. K-ras activating mutations play a key role in neoplastic progression and are particularly prevalent in colorectal, pancreatic, and lung cancers. The present study addressed whether the K-ras proto-oncogene displays a tumor suppressor function by comparative analysis of mouse teratomas derived from wild-type embryonic stem (ES) cells, K-ras null (K-ras(-/-)) ES cells, and K-ras(-/-) ES cells that stably reexpress either wild-type K-ras(gly12) or oncogenic K-ras(val12). K-ras(-/-) and K-ras(val12) teratomas were significantly larger than teratomas that expressed wild-type K-ras, contained significantly higher proportions of undifferentiated embryonal carcinoma-like cells, and showed significantly increased mitotic activity. However, K-ras(val12) but not K-ras(-/-) teratomas exhibited significantly higher levels of apoptosis than wild-type teratomas. K-ras(-/-) and K-ras(val12) ES cells showed a higher capacity for stem cell self-renewal in vitro compared with wild-type ES cells, and reexpression of K-ras(gly12) in K-ras(-/-) ES cells restored the K-ras(-/-) phenotype to wild-type values. Thus, in view of evidence that tumors can derive from tissue stem cells and that tumors harbor "cancer stem cells," aberrant K-ras expression could promote neoplastic progression by increasing their capacity for self-renewal.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Teratoma
/
Genes Supressores de Tumor
/
Genes ras
Limite:
Animals
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Reino Unido