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Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression
BACKGROUND: Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion. METHODS: In this study, we utilize hu...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050851/ https://www.ncbi.nlm.nih.gov/pubmed/21320340 http://dx.doi.org/10.1186/1471-2407-11-69 |
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author | Zhang, Yi Gonzalez, Rachel M Zangar, Richard C |
author_facet | Zhang, Yi Gonzalez, Rachel M Zangar, Richard C |
author_sort | Zhang, Yi |
collection | PubMed |
description | BACKGROUND: Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion. METHODS: In this study, we utilize human epithelial mammary cell (HMEC) lines that were engineered to express different levels of HER1, HER2 and HER3. Using an ELISA microarray platform, we evaluate the effects of epidermal growth factor family receptor (HER) expression on protein secretion in the HMEC lines upon initiation of HER1 receptor activation. The secreted proteins include three HER1 ligands, interleukins 1α and 18, RANTES, vascular-endothelial and platelet-derived growth factors, matrix metalloproteases 1, 2 and 9, and the extracellular portion of the HER1 and HER2 proteins. In addition, we investigate whether MAPK/Erk and PI3K/Akt signaling regulate protein secretion in these cell lines and if so, whether the involvement of HER2 or HER3 receptor alters their response to MAPK/Erk and PI3K/Akt signal pathway inhibition in terms of protein secretion. RESULTS: Differential expression of HER2 and HER3 receptors alters the secretion of a variety of growth factors, cytokines, and proteases. Some alterations in protein secretion are still observed when MAPK/Erk or PI3K/Akt signaling is inhibited. CONCLUSION: This study suggests that HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins. |
format | Text |
id | pubmed-3050851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30508512011-03-09 Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression Zhang, Yi Gonzalez, Rachel M Zangar, Richard C BMC Cancer Research Article BACKGROUND: Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion. METHODS: In this study, we utilize human epithelial mammary cell (HMEC) lines that were engineered to express different levels of HER1, HER2 and HER3. Using an ELISA microarray platform, we evaluate the effects of epidermal growth factor family receptor (HER) expression on protein secretion in the HMEC lines upon initiation of HER1 receptor activation. The secreted proteins include three HER1 ligands, interleukins 1α and 18, RANTES, vascular-endothelial and platelet-derived growth factors, matrix metalloproteases 1, 2 and 9, and the extracellular portion of the HER1 and HER2 proteins. In addition, we investigate whether MAPK/Erk and PI3K/Akt signaling regulate protein secretion in these cell lines and if so, whether the involvement of HER2 or HER3 receptor alters their response to MAPK/Erk and PI3K/Akt signal pathway inhibition in terms of protein secretion. RESULTS: Differential expression of HER2 and HER3 receptors alters the secretion of a variety of growth factors, cytokines, and proteases. Some alterations in protein secretion are still observed when MAPK/Erk or PI3K/Akt signaling is inhibited. CONCLUSION: This study suggests that HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins. BioMed Central 2011-02-14 /pmc/articles/PMC3050851/ /pubmed/21320340 http://dx.doi.org/10.1186/1471-2407-11-69 Text en Copyright ©2011 Zhang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Yi Gonzalez, Rachel M Zangar, Richard C Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title | Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title_full | Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title_fullStr | Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title_full_unstemmed | Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title_short | Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression |
title_sort | protein secretion in human mammary epithelial cells following her1 receptor activation: influence of her2 and her3 expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050851/ https://www.ncbi.nlm.nih.gov/pubmed/21320340 http://dx.doi.org/10.1186/1471-2407-11-69 |
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