Interaction between the bone morphogenetic proteins and Ras MAP-kinase signalling pathways in lung cancer

Bone morphogenetic proteins (BMPs) are an integral component of the TGFbeta superfamily, responsible for regulation of cell proliferation, differentiation, migration and programmed cell death in a variety of cell types. The BMPs transduce their signals directly through the SMAD family of proteins bu...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2005-10, Vol.93 (8), p.949-952
Main Authors: KRAUNZ, K. S, NELSON, H. H, LIU, M, WIENCKE, J. K, KELSEY, K. T
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bone Morphogenetic Protein 3
Bone Morphogenetic Protein 6
Bone Morphogenetic Proteins - metabolism
Bone Morphogenetic Proteins - physiology
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - physiopathology
Cell Transformation, Neoplastic
Epigenesis, Genetic
Gene Expression Regulation
Genes, ras - genetics
Genetics and Genomics
Growth Differentiation Factor 10
Humans
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - physiopathology
Medical sciences
Methylation
Mutation
Pneumology
Polymerase Chain Reaction
ras Proteins - physiology
Signal Transduction - physiology
Tumor Cells, Cultured
Tumors
Tumors of the respiratory system and mediastinum
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bone morphogenetic proteins (BMPs) are an integral component of the TGFbeta superfamily, responsible for regulation of cell proliferation, differentiation, migration and programmed cell death in a variety of cell types. The BMPs transduce their signals directly through the SMAD family of proteins but they also have been reported to interact with the MAPK and Erk pathways. Inactivation of the BMP pathway genes has been implicated as important in several cancers. Recent work has shown that BMP3b is epigenetically inactivated in cancer and suggests that BMP6 can be epigenetically inactivated. We investigated whether BMP6 is epigenetically inactivated in cell lines and whether BMP3b and BMP6 are epigenetically inactivated in non-small-cell lung cancer (NSCLC). We also studied the relationship between BMP methylation and k-ras mutation. Here, we demonstrate that the BMP3b and BMP6 genes are common targets of epigenetic inactivation in NSCLC, and that they are significantly more likely to be concurrently inactivated (P=0.009). Furthermore, this coinactivation of BMP3b and BMP6 is significantly associated with mutation of k-ras codon 12 in lung cancer (P=0.003); those with a k-ras mutation were six times more likely to have concurrent methylation of these BMP loci. Hence, these data suggest that concurrent inactivation of the BMP and activation of the Ras signalling pathways are important in lung carcinogenesis.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6602790