Increased KIT signalling with up-regulation of cyclin D correlates to accelerated proliferation and shorter disease-free survival in gastrointestinal stromal tumours (GISTs) with KIT exon 11 deletions

The Journal of Pathology
Florian HallerLászló Füzesi

Abstract

Gastrointestinal stromal tumours (GISTs) with deletions in KIT exon 11 are characterized by higher proliferation rates and shorter disease-free survival times, compared to GISTs with KIT exon 11 point mutations. Up-regulation of cyclin D is a crucial event for entry into the G1 phase of the cell cycle, and links mitogenic signalling to cell proliferation. Signalling from activated KIT to cyclin D is directed through the RAS/RAF/ERK, PI3K/AKT/mTOR/EIF4E, and JAK/STATs cascades. ERK and STATs initiate mRNA transcription of cyclin D, whereas EIF4E activation leads to increased translation efficiency and reduced degradation of cyclin D protein. The aim of the current study was to analyse the mRNA and protein expression as well as protein phosphorylation of central hubs of these signalling cascades in primary GISTs, to evaluate whether tumours with KIT exon 11 deletions and point mutations differently utilize these pathways. GISTs with KIT exon 11 deletions had significantly higher mitotic counts, higher proliferation rates, and shorter disease-free survival times. In line with this, they had significantly higher expression of cyclin D on the mRNA and protein level. Furthermore, there was a significantly higher amount of phosphoryla...Continue Reading

References

Oct 6, 1995·The Journal of Biological Chemistry·C AlbaneseR G Pestell
Aug 23, 1996·The Journal of Biological Chemistry·J N LavoieJ Pouysségur
Apr 13, 1999·The American Journal of Surgical Pathology·K SircarR H Riddell
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·B Raught, A C Gingras
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Mar 7, 2000·The American Journal of Pathology·M L LuxJ A Fletcher
Apr 12, 2001·Genes & Development·A C GingrasN Sonenberg
Sep 14, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Samuel SingerJonathan A Fletcher
Dec 3, 2002·Gene·Olivier Coqueret
Apr 17, 2003·Molecular and Cellular Biology·Perry M ChanRobert Rottapel
May 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gunhild SommerPeter Besmer
Aug 15, 2003·International Journal of Cancer. Journal International Du Cancer·Eva WardelmannSabine Merkelbach-Bruse
Sep 23, 2003·Journal of Cellular Physiology·Valentina CalòAntonio Russo
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichJonathan A Fletcher
Dec 19, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jerzy LasotaMarkku Miettinen
May 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cristina R AntonescuPeter Besmer
Dec 31, 2004·Stem Cells·Johan LennartssonR Shivakrupa
Aug 3, 2005·Cancer Research·Brian P RubinJessica Woodell
Sep 1, 2005·Biochemical and Biophysical Research Communications·Robert Roskoski
Sep 2, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Javier MartínUNKNOWN Spanish Group for Sarcoma Research
Sep 17, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Florian HallerLászló Füzesi
Oct 18, 2005·Biochemical and Biophysical Research Communications·Robert Roskoski
Nov 17, 2005·Oncogene·Davide Ruggero, Nahum Sonenberg
May 16, 2006·Gastroenterology·Johanna AnderssonBengt Nilsson
Dec 26, 2006·Biochimica Et Biophysica Acta·Jean-Claude ChambardPhilippe Lenormand
Feb 20, 2007·Proteomics·Christian LoebkeUlrike Korf
Jul 17, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jerzy LasotaMarkku Miettinen
Aug 4, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Florian HallerLászló Füzesi
Feb 5, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jerzy LasotaMarkku Miettinen
Mar 13, 2008·European Journal of Gastroenterology & Hepatology·Silke CameronGiuliano Ramadori

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Citations

Aug 4, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yu-Ching WeiHsuan-Ying Huang
Apr 8, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eirini PectasidesAmanda Psyrri
Oct 1, 2009·Proteomics. Clinical Applications·Ulrike KorfAnnemarie Poustka
May 27, 2011·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Hidetaka YamamotoYoshinao Oda
Aug 30, 2012·British Journal of Cancer·F BertucciD Birnbaum
Nov 6, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hsuan-Ying HuangChien-Feng Li

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