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Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients
Germline and somatic mutations play a crucial role in breast cancer (BC), driving the initiation, progression, response to therapy and outcome of the disease. Hormonal therapy is limited to patients with tumors expressing steroid hormone receptors, such as estrogen receptor (ER), nevertheless resist...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041993/ https://www.ncbi.nlm.nih.gov/pubmed/27034161 http://dx.doi.org/10.18632/oncotarget.8417 |
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author | Griseri, Paola Garrone, Ornella Lo Sardo, Alessandra Monteverde, Martino Rusmini, Marta Tonissi, Federica Merlano, Marco Bruzzi, Paolo Lo Nigro, Cristiana Ceccherini, Isabella |
author_facet | Griseri, Paola Garrone, Ornella Lo Sardo, Alessandra Monteverde, Martino Rusmini, Marta Tonissi, Federica Merlano, Marco Bruzzi, Paolo Lo Nigro, Cristiana Ceccherini, Isabella |
author_sort | Griseri, Paola |
collection | PubMed |
description | Germline and somatic mutations play a crucial role in breast cancer (BC), driving the initiation, progression, response to therapy and outcome of the disease. Hormonal therapy is limited to patients with tumors expressing steroid hormone receptors, such as estrogen receptor (ER), nevertheless resistance often limits its success. The RET gene is known to be involved in neurocristopathies such as Hirschsprung disease and Multiple Endocrine Neoplasia type 2, in the presence of loss-of-function and gain-of-function mutations, respectively. More recently, RET over-expression has emerged as a new player in ER-positive (ER+) BC, and as a potential target to enhance sensitivity and avoid resistance to tamoxifen therapy. Therefore, targeting the RET pathway may lead to new therapies in ER+ BC. To this end, we have investigated the molecular mechanisms which underlie RET overexpression and its possible modulation in two BC cell lines, MCF7 and T47D, showing different RET expression levels. Moreover, we have carried out a pilot association study in 93 ER+ BC patients. Consistent with the adverse role of RET over-expression in BC, increased overall survival was observed in carriers of the variant allele of SNP rs2435357, a RET polymorphism already known to be associated with reduced RET expression. |
format | Online Article Text |
id | pubmed-5041993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50419932016-10-10 Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients Griseri, Paola Garrone, Ornella Lo Sardo, Alessandra Monteverde, Martino Rusmini, Marta Tonissi, Federica Merlano, Marco Bruzzi, Paolo Lo Nigro, Cristiana Ceccherini, Isabella Oncotarget Research Paper Germline and somatic mutations play a crucial role in breast cancer (BC), driving the initiation, progression, response to therapy and outcome of the disease. Hormonal therapy is limited to patients with tumors expressing steroid hormone receptors, such as estrogen receptor (ER), nevertheless resistance often limits its success. The RET gene is known to be involved in neurocristopathies such as Hirschsprung disease and Multiple Endocrine Neoplasia type 2, in the presence of loss-of-function and gain-of-function mutations, respectively. More recently, RET over-expression has emerged as a new player in ER-positive (ER+) BC, and as a potential target to enhance sensitivity and avoid resistance to tamoxifen therapy. Therefore, targeting the RET pathway may lead to new therapies in ER+ BC. To this end, we have investigated the molecular mechanisms which underlie RET overexpression and its possible modulation in two BC cell lines, MCF7 and T47D, showing different RET expression levels. Moreover, we have carried out a pilot association study in 93 ER+ BC patients. Consistent with the adverse role of RET over-expression in BC, increased overall survival was observed in carriers of the variant allele of SNP rs2435357, a RET polymorphism already known to be associated with reduced RET expression. Impact Journals LLC 2016-03-28 /pmc/articles/PMC5041993/ /pubmed/27034161 http://dx.doi.org/10.18632/oncotarget.8417 Text en Copyright: © 2016 Griseri 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 Griseri, Paola Garrone, Ornella Lo Sardo, Alessandra Monteverde, Martino Rusmini, Marta Tonissi, Federica Merlano, Marco Bruzzi, Paolo Lo Nigro, Cristiana Ceccherini, Isabella Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title | Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title_full | Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title_fullStr | Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title_full_unstemmed | Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title_short | Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients |
title_sort | genetic and epigenetic factors affect ret gene expression in breast cancer cell lines and influence survival in patients |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041993/ https://www.ncbi.nlm.nih.gov/pubmed/27034161 http://dx.doi.org/10.18632/oncotarget.8417 |
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