Details

Autor(en) / Beteiligte

• Buchholz, Malte
• Schatz, Alexandra
• Wagner, Martin
• Michl, Patrick
• Linhart, Thomas
• Adler, Guido
• Gress, Thomas M
• Ellenrieder, Volker

Titel

Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway

Ist Teil von

• The EMBO journal, 2006-08, Vol.25 (15), p.3714-3724

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2006

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• The nuclear factor of activated T cell (NFAT) proteins are a family of Ca2+/calcineurin‐responsive transcription factors primarily recognized for their central roles in T lymphocyte activation and cardiac valve development. We demonstrate that NFATc1 is commonly overexpressed in pancreatic carcinomas and enhances the malignant potential of tumor cells through transcriptional activation of the c‐myc oncogene. Activated NFATc1 directly binds to a specific element within the proximal c‐myc promoter and upregulates c‐myc transcription, ultimately resulting in increased cell proliferation and enhanced anchorage‐independent growth. Conversely, c‐myc transcription and anchorage‐dependent and ‐independent cell growth is significantly attenuated by inhibition of Ca2+/calcineurin signaling or siRNA‐mediated knock down of NFATc1 expression. Together, these results demonstrate that ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway is an important mechanism of oncogenic c‐myc activation in pancreatic cancer.