Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation

Rebecca G. Watts, Chuanshu Huang, Matthew R. Young, Jian-Jian Li, Zigang Dong, William D. Pennie, Nancy H. Colburn

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

The mitogen activated protein (MAP) kinases or extracellular signal-regulated kinases (Erks) are activated in response to Ras expression or exposure to tumor promoters or to growth factors, and have been implicated in AP-1 transactivation in some models. We have shown that tumor promoter induced activation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model/. Jun and Fos family protein levels have been found not to be limiting for AP-1 response. The present study asks whether activation of Erks1 and 2 is required for AP-1 transactivation and transformation of JB6 cells and whether Erks might be targeted for cancer prevention. Expression of either of two different dominant negative kinase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells substantially inhibited the tumor promoter induced activation of Erks1 and 2 and of AP-1 measured by a collagenase-luciferase reporter. Multiple mutant Erk2 expressing clonal lines were also rendered non-responsive to induced neoplastic transformation. These observations, together with our recent finding attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and/or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progression model, and suggest the utility of Erks as a prevention target.

Original languageEnglish (US)
Pages (from-to)3493-3498
Number of pages6
JournalOncogene
Volume17
Issue number26
StatePublished - Dec 31 1998
Externally publishedYes

Keywords

  • MAP kinases
  • Neoplastic transformation
  • Transcription factors
  • Tumor promotion

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Watts, R. G., Huang, C., Young, M. R., Li, J-J., Dong, Z., Pennie, W. D., & Colburn, N. H. (1998). Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation. Oncogene, 17(26), 3493-3498.