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Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types

Background: There is extensive scientific evidence that radiation therapy (RT) is a crucial treatment, either alone or in combination with other treatment modalities, for many types of cancer, including breast cancer (BC). BC is a heterogeneous disease at both clinical and molecular levels, presenti...

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Autores principales: Bravatà, Valentina, Cava, Claudia, Minafra, Luigi, Cammarata, Francesco Paolo, Russo, Giorgio, Gilardi, Maria Carla, Castiglioni, Isabella, Forte, Giusi Irma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979377/
https://www.ncbi.nlm.nih.gov/pubmed/29617354
http://dx.doi.org/10.3390/ijms19041084
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author Bravatà, Valentina
Cava, Claudia
Minafra, Luigi
Cammarata, Francesco Paolo
Russo, Giorgio
Gilardi, Maria Carla
Castiglioni, Isabella
Forte, Giusi Irma
author_facet Bravatà, Valentina
Cava, Claudia
Minafra, Luigi
Cammarata, Francesco Paolo
Russo, Giorgio
Gilardi, Maria Carla
Castiglioni, Isabella
Forte, Giusi Irma
author_sort Bravatà, Valentina
collection PubMed
description Background: There is extensive scientific evidence that radiation therapy (RT) is a crucial treatment, either alone or in combination with other treatment modalities, for many types of cancer, including breast cancer (BC). BC is a heterogeneous disease at both clinical and molecular levels, presenting distinct subtypes linked to the hormone receptor (HR) status and associated with different clinical outcomes. The aim of this study was to assess the molecular changes induced by high doses of ionizing radiation (IR) on immortalized and primary BC cell lines grouped according to Human epidermal growth factor receptor (HER2), estrogen, and progesterone receptors, to study how HR status influences the radiation response. Our genomic approach using in vitro and ex-vivo models (e.g., primary cells) is a necessary first step for a translational study to describe the common driven radio-resistance features associated with HR status. This information will eventually allow clinicians to prescribe more personalized total doses or associated targeted therapies for specific tumor subtypes, thus enhancing cancer radio-sensitivity. Methods: Nontumorigenic (MCF10A) and BC (MCF7 and MDA-MB-231) immortalized cell lines, as well as healthy (HMEC) and BC (BCpc7 and BCpcEMT) primary cultures, were divided into low grade, high grade, and healthy groups according to their HR status. At 24 h post-treatment, the gene expression profiles induced by two doses of IR treatment with 9 and 23 Gy were analyzed by cDNA microarray technology to select and compare the differential gene and pathway expressions among the experimental groups. Results: We present a descriptive report of the substantial alterations in gene expression levels and pathways after IR treatment in both immortalized and primary cell cultures. Overall, the IR-induced gene expression profiles and pathways appear to be cell-line dependent. The data suggest that some specific gene and pathway signatures seem to be linked to HR status. Conclusions: Genomic biomarkers and gene-signatures of specific tumor subtypes, selected according to their HR status and molecular features, could facilitate personalized biological-driven RT treatment planning alone and in combination with targeted therapies.
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spelling pubmed-59793772018-06-10 Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types Bravatà, Valentina Cava, Claudia Minafra, Luigi Cammarata, Francesco Paolo Russo, Giorgio Gilardi, Maria Carla Castiglioni, Isabella Forte, Giusi Irma Int J Mol Sci Article Background: There is extensive scientific evidence that radiation therapy (RT) is a crucial treatment, either alone or in combination with other treatment modalities, for many types of cancer, including breast cancer (BC). BC is a heterogeneous disease at both clinical and molecular levels, presenting distinct subtypes linked to the hormone receptor (HR) status and associated with different clinical outcomes. The aim of this study was to assess the molecular changes induced by high doses of ionizing radiation (IR) on immortalized and primary BC cell lines grouped according to Human epidermal growth factor receptor (HER2), estrogen, and progesterone receptors, to study how HR status influences the radiation response. Our genomic approach using in vitro and ex-vivo models (e.g., primary cells) is a necessary first step for a translational study to describe the common driven radio-resistance features associated with HR status. This information will eventually allow clinicians to prescribe more personalized total doses or associated targeted therapies for specific tumor subtypes, thus enhancing cancer radio-sensitivity. Methods: Nontumorigenic (MCF10A) and BC (MCF7 and MDA-MB-231) immortalized cell lines, as well as healthy (HMEC) and BC (BCpc7 and BCpcEMT) primary cultures, were divided into low grade, high grade, and healthy groups according to their HR status. At 24 h post-treatment, the gene expression profiles induced by two doses of IR treatment with 9 and 23 Gy were analyzed by cDNA microarray technology to select and compare the differential gene and pathway expressions among the experimental groups. Results: We present a descriptive report of the substantial alterations in gene expression levels and pathways after IR treatment in both immortalized and primary cell cultures. Overall, the IR-induced gene expression profiles and pathways appear to be cell-line dependent. The data suggest that some specific gene and pathway signatures seem to be linked to HR status. Conclusions: Genomic biomarkers and gene-signatures of specific tumor subtypes, selected according to their HR status and molecular features, could facilitate personalized biological-driven RT treatment planning alone and in combination with targeted therapies. MDPI 2018-04-04 /pmc/articles/PMC5979377/ /pubmed/29617354 http://dx.doi.org/10.3390/ijms19041084 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bravatà, Valentina
Cava, Claudia
Minafra, Luigi
Cammarata, Francesco Paolo
Russo, Giorgio
Gilardi, Maria Carla
Castiglioni, Isabella
Forte, Giusi Irma
Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title_full Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title_fullStr Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title_full_unstemmed Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title_short Radiation-Induced Gene Expression Changes in High and Low Grade Breast Cancer Cell Types
title_sort radiation-induced gene expression changes in high and low grade breast cancer cell types
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979377/
https://www.ncbi.nlm.nih.gov/pubmed/29617354
http://dx.doi.org/10.3390/ijms19041084
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