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Molecular Characterization of Lung Dysplasia Induced by c-Raf-1
BACKGROUND: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We employed laser microdissection to harvest c-Raf1- induced dyspl...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681412/ https://www.ncbi.nlm.nih.gov/pubmed/19529782 http://dx.doi.org/10.1371/journal.pone.0005637 |
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author | Rohrbeck, Astrid Müller, Volker Steffen Borlak, Jürgen |
author_facet | Rohrbeck, Astrid Müller, Volker Steffen Borlak, Jürgen |
author_sort | Rohrbeck, Astrid |
collection | PubMed |
description | BACKGROUND: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We employed laser microdissection to harvest c-Raf1- induced dysplastic as opposed to transgenic but otherwise morphologically unaltered epithelium and compared findings to non-transgenic lung. We then employed microarrays to search genome wide for gene regulatory networks. A total of 120 and 287 genes were significantly regulated, respectively. Dysplasia was exclusive associated with up-regulation of genes coding for cell growth and proliferation, cell-to-cell signalling and interaction, lipid metabolism, development, and cancer. Likewise, when dysplasia was compared with non-transgenic cells up-regulation of cancer associated genes, tight junction proteins, xenobiotic defence and developmental regulators was observed. Further, in a comparison of the data sets of dysplasia vs transgenic and dysplasia vs non-transgenic 114 genes were regulated in common. We additionally confirmed regulation of some genes by immunohistochemistry and therefore demonstrate good concordance between gene regulation and coded protein. CONCLUSION: Our study identified transcriptional networks at successive stages of tumor-development, i.e. from histological unaltered but transgenic lungs to nuclear atypia. Our SP-C/c-raf transgenic mouse model revealed interesting and novel candidate genes and pathways that provide clues on the mechanism forcing respiratory epithelium into dysplasia and subsequently cancer, some of which might also be useful in the molecular imaging and flagging of early stages of disease. |
format | Text |
id | pubmed-2681412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26814122009-05-25 Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 Rohrbeck, Astrid Müller, Volker Steffen Borlak, Jürgen PLoS One Research Article BACKGROUND: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We employed laser microdissection to harvest c-Raf1- induced dysplastic as opposed to transgenic but otherwise morphologically unaltered epithelium and compared findings to non-transgenic lung. We then employed microarrays to search genome wide for gene regulatory networks. A total of 120 and 287 genes were significantly regulated, respectively. Dysplasia was exclusive associated with up-regulation of genes coding for cell growth and proliferation, cell-to-cell signalling and interaction, lipid metabolism, development, and cancer. Likewise, when dysplasia was compared with non-transgenic cells up-regulation of cancer associated genes, tight junction proteins, xenobiotic defence and developmental regulators was observed. Further, in a comparison of the data sets of dysplasia vs transgenic and dysplasia vs non-transgenic 114 genes were regulated in common. We additionally confirmed regulation of some genes by immunohistochemistry and therefore demonstrate good concordance between gene regulation and coded protein. CONCLUSION: Our study identified transcriptional networks at successive stages of tumor-development, i.e. from histological unaltered but transgenic lungs to nuclear atypia. Our SP-C/c-raf transgenic mouse model revealed interesting and novel candidate genes and pathways that provide clues on the mechanism forcing respiratory epithelium into dysplasia and subsequently cancer, some of which might also be useful in the molecular imaging and flagging of early stages of disease. Public Library of Science 2009-05-20 /pmc/articles/PMC2681412/ /pubmed/19529782 http://dx.doi.org/10.1371/journal.pone.0005637 Text en Rohrbeck et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rohrbeck, Astrid Müller, Volker Steffen Borlak, Jürgen Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title | Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title_full | Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title_fullStr | Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title_full_unstemmed | Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title_short | Molecular Characterization of Lung Dysplasia Induced by c-Raf-1 |
title_sort | molecular characterization of lung dysplasia induced by c-raf-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681412/ https://www.ncbi.nlm.nih.gov/pubmed/19529782 http://dx.doi.org/10.1371/journal.pone.0005637 |
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