The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells

Jung Sun Kim, Byung Soo Kim, Jiha Kim, Choon Sik Park, Il Yup Chung

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Nanog is a key determinant that maintains self-renewal and pluripotency of embryonic stem cells and represses their differentiation to endoderm. In this study, we examined the regulation of Nanog expression by phosphoinositide-3- kinase (PI3K)/Akt pathway during retinoic acid (RA)-induced differentiation of F9 embryonic carcinoma cells. Nanog protein expression was transiently upregulated up to 6 h after RA treatment and then declined. In agreement, a murine Nanog promoter reporter assay revealed that promoter activity increased during early stage of differentiation, but decreased when F9 cells became fully differentiated. RA treatment of F9 cells also led to a transient and parallel increase in both Akt and glycogen synthase kinase 3β phosphorylations. Nanog expression was diminished in the early stage by LY294002, a PI3K inhibitor, but was not affected in the late stage despite considerable inhibition of Akt phosphorylation and endoderm marker expression by the inhibitor. These data suggest that RA-induced PI3K/Akt activation in the early stage of differentiation is required for Nanog expression, which becomes independent of PI3K/Akt signaling once the differentiation is established. Thus, Nanog expression appears to be differently regulated by the PI3K/Akt pathway depending on differentiation stage.

Original languageEnglish (US)
Pages (from-to)1117-1125
Number of pages9
JournalArchives of Pharmacal Research
Volume33
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Embryonic stem cells
  • Endoderm
  • F9 cells
  • Nanog
  • Phosphoinositide-3-kinase
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells'. Together they form a unique fingerprint.

Cite this