Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling

Abstract Expression of the low-density lipoprotein receptor (LDLR) has been shown to play a critical role in hypercholesterolemia-associated breast cancer growth and is associated with shorter recurrence-free survival in human breast cancer studies. We sought to identify how circulating LDL choleste...

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Autores principales:	Tiffany Scully, Nathan Kase, Emily J. Gallagher, Derek LeRoith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4637f21548d947e5b1af8ade15841430
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spelling	oai:doaj.org-article:4637f21548d947e5b1af8ade158414302021-12-02T17:19:15ZRegulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling10.1038/s41598-021-97327-y2045-2322https://doaj.org/article/4637f21548d947e5b1af8ade158414302021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97327-yhttps://doaj.org/toc/2045-2322Abstract Expression of the low-density lipoprotein receptor (LDLR) has been shown to play a critical role in hypercholesterolemia-associated breast cancer growth and is associated with shorter recurrence-free survival in human breast cancer studies. We sought to identify how circulating LDL cholesterol and tumor LDLR might accelerate oncogenic processes by determining whether increased LDLR expression and cholesterol uptake are associated with the activation of the epidermal growth factor receptor (EGFR) signaling pathway in triple negative breast cancer (TNBC) cell lines. EGF stimulation of MDA-MB-468 (MDA468) cells activated p44/42MAPK (MAPK), increased expression of LDLR, and fluorescent LDL cholesterol uptake. However, stimulation of MDA-MB-231 (MDA231) cells with EGF did not lead to increased expression of LDLR despite inducing phosphorylation of EGFR. Inhibition of MAPK using UO126 in MDA231 cells reduced LDLR expression, and in MDA468 cells, UO126 impaired the LDLR increase in response to EGF. MDA468 cells exposed to the transcription inhibitor, Actinomycin, prior to treatment with EGF showed reduced degradation of LDLR mRNA compared to vehicle-treated cells. Our results suggest that the EGF-associated increase in LDLR protein expression is cell line-specific. The common pathway regulating LDLR expression was MAPK in both TNBC cell lines.Tiffany ScullyNathan KaseEmily J. GallagherDerek LeRoithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiffany Scully Nathan Kase Emily J. Gallagher Derek LeRoith Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
description	Abstract Expression of the low-density lipoprotein receptor (LDLR) has been shown to play a critical role in hypercholesterolemia-associated breast cancer growth and is associated with shorter recurrence-free survival in human breast cancer studies. We sought to identify how circulating LDL cholesterol and tumor LDLR might accelerate oncogenic processes by determining whether increased LDLR expression and cholesterol uptake are associated with the activation of the epidermal growth factor receptor (EGFR) signaling pathway in triple negative breast cancer (TNBC) cell lines. EGF stimulation of MDA-MB-468 (MDA468) cells activated p44/42MAPK (MAPK), increased expression of LDLR, and fluorescent LDL cholesterol uptake. However, stimulation of MDA-MB-231 (MDA231) cells with EGF did not lead to increased expression of LDLR despite inducing phosphorylation of EGFR. Inhibition of MAPK using UO126 in MDA231 cells reduced LDLR expression, and in MDA468 cells, UO126 impaired the LDLR increase in response to EGF. MDA468 cells exposed to the transcription inhibitor, Actinomycin, prior to treatment with EGF showed reduced degradation of LDLR mRNA compared to vehicle-treated cells. Our results suggest that the EGF-associated increase in LDLR protein expression is cell line-specific. The common pathway regulating LDLR expression was MAPK in both TNBC cell lines.
format	article
author	Tiffany Scully Nathan Kase Emily J. Gallagher Derek LeRoith
author_facet	Tiffany Scully Nathan Kase Emily J. Gallagher Derek LeRoith
author_sort	Tiffany Scully
title	Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
title_short	Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
title_full	Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
title_fullStr	Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
title_full_unstemmed	Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
title_sort	regulation of low-density lipoprotein receptor expression in triple negative breast cancer by egfr-mapk signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4637f21548d947e5b1af8ade15841430
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Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling

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