Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling.

ABSTRACT: The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. Suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1. KLF4-induced transformation was suppressed by knockdown of endogenous Notch1 using siRNA or an inhibitor of gamma-secretase. Chromatin immunoprecipitation assay shows that KLF4 binds to the proximal Notch1 promoter in human mammary epithelial cells, and siRNA-mediated suppression of KLF4 in human mammary cancer cells results

SUBMITTER: Liu Z 

PROVIDER: S-EPMC2795010 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature