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Overexpression of c ‐myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca 2+ /calcineurin signaling pathway
Author(s) -
Buchholz Malte,
Schatz Alexandra,
Wagner Martin,
Michl Patrick,
Linhart Thomas,
Adler Guido,
Gress Thomas M,
Ellenrieder Volker
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601246
Subject(s) - medicine , biology
The nuclear factor of activated T cell (NFAT) proteins are a family of Ca 2+ /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 Ca 2+ /calcineurin signaling or siRNA‐mediated knock down of NFATc1 expression. Together, these results demonstrate that ectopic activation of NFATc1 and the Ca 2+ /calcineurin signaling pathway is an important mechanism of oncogenic c ‐myc activation in pancreatic cancer.