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

K. S. Kraunz, H. H. Nelson, M. Liu, J. K. Wiencke, K. T. Kelsey

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53 Scopus citations


Bone morphogenetic proteins (BMPs) are an integral component of the TGFΒ 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.

Original languageEnglish (US)
Pages (from-to)949-952
Number of pages4
JournalBritish Journal of Cancer
Issue number8
StatePublished - Oct 17 2005

Bibliographical note

Funding Information:
This work was supported by CA100679, CA078609 and ES00002.


  • Bone morphogenetic proteins
  • Epigenetic inactivation
  • Methylation
  • Non-small-cell lung cancer
  • k-ras mutation


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