Carolin Schild and Matthias Wirth contributed equally to this work.
PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells†
Article first published online: 14 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 48, Issue 12, pages 1149–1158, December 2009
How to Cite
Schild, C., Wirth, M., Reichert, M., Schmid, R. M., Saur, D. and Schneider, G. (2009), PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells. Mol. Carcinog., 48: 1149–1158. doi: 10.1002/mc.20569
- Issue published online: 23 NOV 2009
- Article first published online: 14 JUL 2009
- Manuscript Accepted: 11 JUN 2009
- Manuscript Revised: 29 MAY 2009
- Manuscript Received: 21 MAR 2009
- pancreatic cancer;
Phosphatidylinositol 3-kinase (PI3K) signaling controls survival and proliferation of cancer cells and is activated in around 60% of pancreatic ductal adenocarcinomas (PDACs). Although not entirely clarified, PI3K signaling is linked to cell cycle progression of PDAC cells. In this study we demonstrate that PI3K signaling controls transcription of the E2F1 gene and show that E2F1 is essential for S-phase progression of PDAC cells. On the molecular level, PI3K signaling controls c-myc protein abundance in a glycogen synthase kinase-3 (GSK3)-dependent fashion. c-myc binds to the E-box of the E2F1 gene in PDAC cells and this binding is under control of the PI3K-signaling pathway. Together, we demonstrate that PI3K–GSK3-dependent control of c-myc protein expression is connected to the transcription of the E2F1 gene in PDAC cells, leading to S-phase progression of the cell cycle. © 2009 Wiley-Liss, Inc.