NFAT3 is specifically required for TNF-α-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Cyclooxygenase 2
  • Epidermis
  • Gene Expression Regulation, Enzymologic
  • NFATC Transcription Factors
  • Tumor Necrosis Factor-alpha

abstract

  • NFAT family is recognized as a transcription factor for inflammation regulation by inducing the expression of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), the key mediator of inflammation, which was reported to induce cell transformation in mouse epidermal Cl41 cells. In this study, we demonstrated that TNF-alpha was able to induce NFAT activation, as well as the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The induction of COX-2 by TNF-alpha was abolished by knockdown of NFAT3 with its siRNA, while the induction of iNOS was not effected. Moreover, TNF-alpha-induced anchorage-independent cell growth was significantly inhibited by NFAT3 siRNA and cyclosporine A, a chemical inhibitor for the calcineurin/NFAT pathway, which suggests the importance of NFAT3 in regulating TNF-alpha-induced anchorage-independent cell growth. Consequently, impairment of COX-2 by its siRNA or selective inhibitor also inhibited TNF-alpha-induced anchorage-independent cell growth. Taken together, our results indicate that NFAT3 plays an important role in the regulation of TNF-alpha-induced anchorage-independent cell growth, at least partially, by inducing COX-2 expression in Cl41 cells. These findings suggest that NFAT3/cyclooxygenase-2 act as a link between inflammation and carcinogenesis by being involved in the tumor promotion stage.

publication date

  • July 15, 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1242/jcs.03014

PubMed ID

  • 16803872

Additional Document Info

start page

  • 2985

end page

  • 94

volume

  • 119

number

  • 14