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EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3

Pavel S Grudinkin1, Valery V Zenin, Andrey V Kropotov

  • 1Department of Intracellular Signalling and Transport, Institute of Cytology RAS, 194064 St. Petersburg, Russia. paulsg@rbcmail.ru

European Journal of Cell Biology
|July 25, 2007
PubMed

Insights

Epidermal Growth Factor (EGF) normally inhibits A431 cancer cell growth. This study reveals that Signal Transducer and Activator of Transcription 1 (STAT1) is crucial for this EGF-induced apoptosis, with STAT1 phosphorylation mediating the effect.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • High concentrations of Epidermal Growth Factor (EGF) inhibit the growth of human epidermoid carcinoma cells (A431).
  • The transcription factor Signal Transducer and Activator of Transcription 1 (STAT1) is implicated in mediating this EGF-induced growth inhibition.

Purpose of the Study:

  • To investigate the role of STAT1 in EGF-mediated growth inhibition and apoptosis in A431 cells.
  • To determine if STAT1 phosphorylation is essential for the anti-proliferative effects of EGF.

Main Methods:

  • Generated EGF-resistant A431 sub-clones and reintroduced wild-type or mutant STAT1.
  • Utilized short hairpin RNA (shRNA) to knock down STAT1 and STAT3 expression in A431 cells.
  • Assessed cell growth, apoptosis, and STAT1/STAT3 tyrosine phosphorylation levels.

Main Results:

  • EGF-resistant cells showed reduced STAT1 expression; reintroducing wild-type STAT1 restored EGF sensitivity.
  • STAT1 knockdown prevented EGF-induced apoptosis and allowed continued cell growth.
  • Blocking Src family kinases reduced STAT1/STAT3 phosphorylation and protected cells from EGF-induced growth inhibition.

Conclusions:

  • Tyrosine-phosphorylated STAT1, not STAT3, is essential for EGF-induced apoptosis in A431 cells.
  • STAT1 plays a critical role in mediating the growth-inhibitory and apoptotic effects of EGF in this cancer cell line.

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