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Oncogenic K-Ras promotes proliferation in quiescent intestinal stem cells.

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.

SUBMITTER: Gierut JJ

PROVIDER: S-EPMC4629819 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Oncogenic K-Ras promotes proliferation in quiescent intestinal stem cells.

Gierut Jessica J JJ Lyons Jesse J Shah Manasvi S MS Genetti Casie C Breault David T DT Haigis Kevin M KM

Stem cell research 20150610 1

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 quiesce ...[more]

PMID: 26079371

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