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Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis

Item Type:Article
Title:Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis
Creators Name:Voorneveld, P.W. and Stache, V. and Jacobs, R.J. and Smolders, E. and Sitters, A.I. and Liesker, A. and Korkmaz, K.S. and Lam, S.M. and De Miranda, N.F.C.C. and Morreau, H. and Kodach, L.L. and Hardwick, J.C.H.
Abstract:Background: The expression of SMAD4, the central component of the transforming growth factor-{beta} (TGF-{beta}) and bone morphogenetic protein (BMP) signalling pathways, is lost in 50% of pancreatic cancers and is associated with a poor survival. Although the TGF-{beta} pathway has been extensively studied and characterised in pancreatic cancer, there is very limited data on BMP signalling, a well-known tumour-suppressor pathway. BMP signalling can be lost not only at the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been described in colorectal cancer. Methods: We performed immunohistochemical analysis of the expression levels of BMP signalling components in pancreatic cancer and correlated these with survival. We also manipulated the activity of BMP signalling in vitro.Results: Reduced expression of BMPRIA is associated with a significantly worse survival, primarily in a subset of SMAD4-positive cancers. In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling in SMAD4-negative cells does not change the proliferation and invasion or leads to an opposite effect. Conclusion: Our data suggest that BMPRIA expression is a good prognostic marker and that the BMP pathway is a potential target for future therapeutic interventions in pancreatic cancer.
Keywords:BMP, SMAD4, BMPRIA, Pancreatic Cancer, Survival
Source:British Journal of Cancer
Publisher:Nature Publishing Group
Page Range:1805-1812
Date:1 October 2013
Additional Information:(c) 2013 Cancer Research UK.
Official Publication:https://doi.org/10.1038/bjc.2013.486
PubMed:View item in PubMed

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