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In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays
Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approache...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808046/ https://www.ncbi.nlm.nih.gov/pubmed/26556871 |
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author | Callari, Maurizio Guffanti, Alessandro Soldà, Giulia Merlino, Giuseppe Fina, Emanuela Brini, Elena Moles, Anna Cappelletti, Vera Daidone, Maria Grazia |
author_facet | Callari, Maurizio Guffanti, Alessandro Soldà, Giulia Merlino, Giuseppe Fina, Emanuela Brini, Elena Moles, Anna Cappelletti, Vera Daidone, Maria Grazia |
author_sort | Callari, Maurizio |
collection | PubMed |
description | Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment. |
format | Online Article Text |
id | pubmed-4808046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48080462016-04-19 In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays Callari, Maurizio Guffanti, Alessandro Soldà, Giulia Merlino, Giuseppe Fina, Emanuela Brini, Elena Moles, Anna Cappelletti, Vera Daidone, Maria Grazia Oncotarget Research Paper Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment. Impact Journals LLC 2015-11-03 /pmc/articles/PMC4808046/ /pubmed/26556871 Text en Copyright: © 2016 Callari et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Callari, Maurizio Guffanti, Alessandro Soldà, Giulia Merlino, Giuseppe Fina, Emanuela Brini, Elena Moles, Anna Cappelletti, Vera Daidone, Maria Grazia In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title | In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title_full | In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title_fullStr | In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title_full_unstemmed | In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title_short | In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays |
title_sort | in-depth characterization of breast cancer tumor-promoting cell transcriptome by rna sequencing and microarrays |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808046/ https://www.ncbi.nlm.nih.gov/pubmed/26556871 |
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