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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 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 t...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361658/ https://www.ncbi.nlm.nih.gov/pubmed/16175182 http://dx.doi.org/10.1038/sj.bjc.6602790 |
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author | Kraunz, K S Nelson, H H Liu, M Wiencke, J K Kelsey, K T |
author_facet | Kraunz, K S Nelson, H H Liu, M Wiencke, J K Kelsey, K T |
author_sort | Kraunz, K S |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2361658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23616582009-09-10 Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer Kraunz, K S Nelson, H H Liu, M Wiencke, J K Kelsey, K T Br J Cancer Genetics and Genomics 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. Nature Publishing Group 2005-10-17 2005-09-20 /pmc/articles/PMC2361658/ /pubmed/16175182 http://dx.doi.org/10.1038/sj.bjc.6602790 Text en Copyright © 2005 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Genetics and Genomics Kraunz, K S Nelson, H H Liu, M Wiencke, J K Kelsey, K T Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title | Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title_full | Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title_fullStr | Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title_full_unstemmed | Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title_short | Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer |
title_sort | interaction between the bone morphogenetic proteins and ras/map-kinase signalling pathways in lung cancer |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361658/ https://www.ncbi.nlm.nih.gov/pubmed/16175182 http://dx.doi.org/10.1038/sj.bjc.6602790 |
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