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Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data

BACKGOUND: The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis. METHODS: We conducted...

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Autores principales: Gorlov, Ivan P, Byun, Jinyoung, Gorlova, Olga Y, Aparicio, Ana M, Efstathiou, Eleni, Logothetis, Christopher J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731785/
https://www.ncbi.nlm.nih.gov/pubmed/19653896
http://dx.doi.org/10.1186/1755-8794-2-48
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author Gorlov, Ivan P
Byun, Jinyoung
Gorlova, Olga Y
Aparicio, Ana M
Efstathiou, Eleni
Logothetis, Christopher J
author_facet Gorlov, Ivan P
Byun, Jinyoung
Gorlova, Olga Y
Aparicio, Ana M
Efstathiou, Eleni
Logothetis, Christopher J
author_sort Gorlov, Ivan P
collection PubMed
description BACKGOUND: The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis. METHODS: We conducted a meta-analysis of gene expression data from 18 gene array datasets targeting transition from normal to localized prostate cancer and from localized to metastatic prostate cancer. We functionally annotated the top 500 differentially expressed genes and identified several candidate pathways associated with prostate tumorigeneses. RESULTS: We found the top differentially expressed genes to be clustered in pathways involving integrin-based cell adhesion: integrin signaling, the actin cytoskeleton, cell death, and cell motility pathways. We also found integrins themselves to be downregulated in the transition from normal prostate tissue to primary localized prostate cancer. Based on the results of this study, we developed a collagen hypothesis of prostate tumorigenesis. According to this hypothesis, the initiating event in prostate tumorigenesis is the age-related decrease in the expression of collagen genes and other genes encoding integrin ligands. This concomitant depletion of integrin ligands leads to the accumulation of ligandless integrin and activation of integrin-associated cell death. To escape integrin-associated death, cells suppress the expression of integrins, which in turn alters the actin cytoskeleton, elevates cell motility and proliferation, and disorganizes prostate histology, contributing to the histologic progression of prostate cancer and its increased metastasizing potential. CONCLUSION: The results of this study suggest that prostate tumor progression is associated with the suppression of integrin-based cell adhesion. Suppression of integrin expression driven by integrin-mediated cell death leads to increased cell proliferation and motility and increased tumor malignancy.
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spelling pubmed-27317852009-08-26 Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data Gorlov, Ivan P Byun, Jinyoung Gorlova, Olga Y Aparicio, Ana M Efstathiou, Eleni Logothetis, Christopher J BMC Med Genomics Research Article BACKGOUND: The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis. METHODS: We conducted a meta-analysis of gene expression data from 18 gene array datasets targeting transition from normal to localized prostate cancer and from localized to metastatic prostate cancer. We functionally annotated the top 500 differentially expressed genes and identified several candidate pathways associated with prostate tumorigeneses. RESULTS: We found the top differentially expressed genes to be clustered in pathways involving integrin-based cell adhesion: integrin signaling, the actin cytoskeleton, cell death, and cell motility pathways. We also found integrins themselves to be downregulated in the transition from normal prostate tissue to primary localized prostate cancer. Based on the results of this study, we developed a collagen hypothesis of prostate tumorigenesis. According to this hypothesis, the initiating event in prostate tumorigenesis is the age-related decrease in the expression of collagen genes and other genes encoding integrin ligands. This concomitant depletion of integrin ligands leads to the accumulation of ligandless integrin and activation of integrin-associated cell death. To escape integrin-associated death, cells suppress the expression of integrins, which in turn alters the actin cytoskeleton, elevates cell motility and proliferation, and disorganizes prostate histology, contributing to the histologic progression of prostate cancer and its increased metastasizing potential. CONCLUSION: The results of this study suggest that prostate tumor progression is associated with the suppression of integrin-based cell adhesion. Suppression of integrin expression driven by integrin-mediated cell death leads to increased cell proliferation and motility and increased tumor malignancy. BioMed Central 2009-08-04 /pmc/articles/PMC2731785/ /pubmed/19653896 http://dx.doi.org/10.1186/1755-8794-2-48 Text en Copyright © 2009 Gorlov et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gorlov, Ivan P
Byun, Jinyoung
Gorlova, Olga Y
Aparicio, Ana M
Efstathiou, Eleni
Logothetis, Christopher J
Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title_full Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title_fullStr Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title_full_unstemmed Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title_short Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
title_sort candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731785/
https://www.ncbi.nlm.nih.gov/pubmed/19653896
http://dx.doi.org/10.1186/1755-8794-2-48
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