Oncogenic K-Ras promotes proliferation in quiescent intestinal stem cells.
Stem Cell Res
; 15(1): 165-71, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26079371
ABSTRACT
K-Ras is a monomeric GTPase that controls cellular and tissue homeostasis. Prior studies demonstrated that mutationally activated K-Ras (K-Ras(G12D)) signals through MEK to promote expansion and hyperproliferation of the highly mitotically active transit-amplifying cells (TACs) in the intestinal crypt. Its effect on normally quiescent stem cells was unknown, however. Here, we have used an H2B-Egfp transgenic system to demonstrate that K-Ras(G12D) accelerates the proliferative kinetics of quiescent intestinal stem cells. As in the TAC compartment, the effect of mutant K-Ras on the quiescent stem cell is dependent upon activation of MEK. Mutant K-Ras is also able to increase self-renewal potential of intestinal stem cells following damage. These results demonstrate that mutant K-Ras can influence intestinal homeostasis on multiple levels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Proteínas Proto-Oncogênicas p21(ras)
/
Intestinos
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos