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

R G Watts1, C Huang, M R Young

  • 1National Cancer Institute-FCRDC, Laboratory of Biochemical Physiology, Frederick, Maryland 21702-1201, USA.

Oncogene
|February 25, 1999
PubMed

Insights

Extracellular signal-regulated kinases (Erks) activation is crucial for AP-1 transactivation and neoplastic transformation in JB6 cells. Targeting Erks may offer a novel strategy for cancer prevention.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Cancer research

Background:

  • Mitogen-activated protein (MAP) kinases, or extracellular signal-regulated kinases (Erks), are activated by growth factors and tumor promoters.
  • Erks have been implicated in AP-1 transactivation, a process vital for neoplastic transformation.
  • Previous studies established that AP-1 activation is necessary for tumor promoter-induced neoplastic transformation in Balb/C JB6 cells.

Purpose of the Study:

  • To investigate the role of Erk1 and Erk2 activation in AP-1 transactivation and neoplastic transformation in JB6 cells.
  • To determine if Erks could serve as potential targets for cancer prevention strategies.

Main Methods:

  • Utilized dominant-negative kinase-inactive Erk2 mutants in transformation-sensitive (P+) JB6 cells.
  • Assessed the impact of Erk2 mutants on Erk1/2 activation and AP-1 activity using a collagenase-luciferase reporter assay.
  • Generated and analyzed clonal lines expressing Erk2 mutants for neoplastic transformation responsiveness.

Main Results:

  • Expression of dominant-negative Erk2 mutants significantly inhibited tumor promoter-induced activation of Erks1/2 and AP-1.
  • JB6 cell lines expressing multiple Erk2 mutants demonstrated a lack of response to induced neoplastic transformation.
  • These findings align with previous observations of AP-1 non-responsiveness linked to Erk deficiency in transformation-resistant cells.

Conclusions:

  • Erk1 and/or Erk2 activation is essential for AP-1 transactivation in the JB6 cell neoplastic progression model.
  • Erk signaling pathways represent a promising target for cancer prevention interventions.

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