Mapping the genetic basis of breast microcalcifications and their role in metastasis

Abstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely...

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Autores principales:	Asif Rizwan, Santosh Kumar Paidi, Chao Zheng, Menglin Cheng, Ishan Barman, Kristine Glunde
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97b89b4877bf426ea038050a5b2191c2
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spelling	oai:doaj.org-article:97b89b4877bf426ea038050a5b2191c22021-12-02T15:07:57ZMapping the genetic basis of breast microcalcifications and their role in metastasis10.1038/s41598-018-29330-92045-2322https://doaj.org/article/97b89b4877bf426ea038050a5b2191c22018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29330-9https://doaj.org/toc/2045-2322Abstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely unknown. In the current work, we have investigated the genetic drivers for the formation of microcalcifications in breast cancer cell lines, and have investigated their involvement in disease progression. We have shown that stable silencing of the Osteopontin (OPN) gene decreased the formation of hydroxyapatite in MDA-MB-231 breast cancer cells in response to osteogenic cocktail. In addition, OPN silencing reduced breast cancer cell migration. Furthermore, breast cancer cells that had spontaneously metastasized to the lungs in a mouse model of breast cancer had largely elevated OPN levels, while circulating tumor cells in the same mouse model contained intermediately increased OPN levels as compared to parental cells. The observed dual roles of the OPN gene reveal the existence of a direct relationship between calcium deposition and the ability of breast cancer cells to metastasize to distant organs, mediated by common genetic factors.Asif RizwanSantosh Kumar PaidiChao ZhengMenglin ChengIshan BarmanKristine GlundeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde Mapping the genetic basis of breast microcalcifications and their role in metastasis
description	Abstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely unknown. In the current work, we have investigated the genetic drivers for the formation of microcalcifications in breast cancer cell lines, and have investigated their involvement in disease progression. We have shown that stable silencing of the Osteopontin (OPN) gene decreased the formation of hydroxyapatite in MDA-MB-231 breast cancer cells in response to osteogenic cocktail. In addition, OPN silencing reduced breast cancer cell migration. Furthermore, breast cancer cells that had spontaneously metastasized to the lungs in a mouse model of breast cancer had largely elevated OPN levels, while circulating tumor cells in the same mouse model contained intermediately increased OPN levels as compared to parental cells. The observed dual roles of the OPN gene reveal the existence of a direct relationship between calcium deposition and the ability of breast cancer cells to metastasize to distant organs, mediated by common genetic factors.
format	article
author	Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde
author_facet	Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde
author_sort	Asif Rizwan
title	Mapping the genetic basis of breast microcalcifications and their role in metastasis
title_short	Mapping the genetic basis of breast microcalcifications and their role in metastasis
title_full	Mapping the genetic basis of breast microcalcifications and their role in metastasis
title_fullStr	Mapping the genetic basis of breast microcalcifications and their role in metastasis
title_full_unstemmed	Mapping the genetic basis of breast microcalcifications and their role in metastasis
title_sort	mapping the genetic basis of breast microcalcifications and their role in metastasis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/97b89b4877bf426ea038050a5b2191c2
work_keys_str_mv	AT asifrizwan mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis AT santoshkumarpaidi mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis AT chaozheng mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis AT menglincheng mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis AT ishanbarman mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis AT kristineglunde mappingthegeneticbasisofbreastmicrocalcificationsandtheirroleinmetastasis
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Mapping the genetic basis of breast microcalcifications and their role in metastasis

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