Differentiation-associated genes regulated by TPA-induced c-Jun expression via a PKC/JNK pathway in KYSE450 cells

Biochem Biophys Res Commun. 2006 Mar 31;342(1):286-92. doi: 10.1016/j.bbrc.2006.01.147. Epub 2006 Feb 6.


A group of potential differentiation-associated genes had been identified by microarray analysis as c-Jun/AP-1 target genes essential for epithelial differentiation program. Our previous study showed that c-Jun/AP-1 could bind and activate these gene promoters in vivo using chromatin immunoprecipitation. To further understand how the mitogen-activated protein kinase signaling pathways regulate AP-1 activity and expression of c-Jun target genes, our strategy was based on the use of 12-o-tetradecanoylophorbol-13-acetate (TPA) and pharmacological reagents to induce or block c-Jun expression. The mRNA and protein expression of these genes increased in response to TPA-induced c-Jun/AP-1 expression. Inhibitors of JNK (SP600125) and PKC (GF109203X) mainly blocked expression and phosphorylation of c-Jun, while inhibition of MEK-ERK activity with PD98059 (an inhibitor of MEK) had little effect. Expression of involucrin and keratin 4 in response to TPA was attenuated by pretreatments with GF109203X and SP600125, but not PD98059, suggesting involvement of PKC and JNK in this response. Taken together, these results suggested that differentiation-associated genes were regulated by TPA-induced c-Jun/AP-1 mainly via a PKC/JNK pathway in esophageal cancer cell line KYSE450.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation* / drug effects
  • Cell Line, Tumor
  • DNA / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Signal Transduction / drug effects*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / drug effects


  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • DNA
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate