Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli

Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli

Prion protein (PrP) is well studied for its pathogenic role in prion disease, but its potential contribution to other pathological processes is less understood. PrP is expressed in a variety of cancers and at least in pancreatic and breast cancers, its expression appears to be associated with poor p...

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Main Authors: Yu, Guohua, Jiang, Liming, Xu, Yuanyuan, Guo, Hongwei, Liu, Huiyan, Zhang, Yi, Yang, Huaiyi, Yuan, Chonggang, Ma, Jiyan
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487893/
id pubmed-3487893
recordtype oai_dc
spelling pubmed-34878932012-11-06 Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli Yu, Guohua Jiang, Liming Xu, Yuanyuan Guo, Hongwei Liu, Huiyan Zhang, Yi Yang, Huaiyi Yuan, Chonggang Ma, Jiyan Research Article Prion protein (PrP) is well studied for its pathogenic role in prion disease, but its potential contribution to other pathological processes is less understood. PrP is expressed in a variety of cancers and at least in pancreatic and breast cancers, its expression appears to be associated with poor prognosis. To understand the role of PrP in breast cancer cells, we knocked down PrP expression in MDA-MB-435 breast cancer cells with small interfering RNA and subjected these cells to a series of analyses. We found that PrP knockdown in these cells does not affect cell proliferation or colony formation, but significantly influences the cellular response to cytotoxic stimuli. Compared to control cells, PrP knockdown cells exhibited an increased susceptibility to serum deprivation induced apoptosis, no change to staurosporine- or paclitaxel-induced cell deaths, and a reduced susceptibility to chemotherapy drug doxorubicin-induced cell death. To understand the mechanism of unexpected role of PrP in exacerbating doxorubicin-induced cytotoxicity, we analyzed cell death related Bcl-2 family proteins. We found that PrP knockdown alters the expression of several Bcl-2 family proteins, correlating with increased resistance to doxorubicin-induced cytotoxicity. Moreover, the enhanced doxorubicin resistance is independent of DNA damage related p53 pathway, but at least partially through the ERK1/2 pathway. Together, our study revealed that silencing PrP in MDA-MB-435 breast cancer cells results in very different responses to various cytotoxic stimuli and ERK1/2 signaling pathway is involved in PrP silencing caused resistance to doxorubicin. Public Library of Science 2012-11-02 /pmc/articles/PMC3487893/ /pubmed/23133614 http://dx.doi.org/10.1371/journal.pone.0048146 Text en © 2012 Yu et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Yu, Guohua
Jiang, Liming
Xu, Yuanyuan
Guo, Hongwei
Liu, Huiyan
Zhang, Yi
Yang, Huaiyi
Yuan, Chonggang
Ma, Jiyan
spellingShingle Yu, Guohua
Jiang, Liming
Xu, Yuanyuan
Guo, Hongwei
Liu, Huiyan
Zhang, Yi
Yang, Huaiyi
Yuan, Chonggang
Ma, Jiyan
Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
author_facet Yu, Guohua
Jiang, Liming
Xu, Yuanyuan
Guo, Hongwei
Liu, Huiyan
Zhang, Yi
Yang, Huaiyi
Yuan, Chonggang
Ma, Jiyan
author_sort Yu, Guohua
title Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
title_short Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
title_full Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
title_fullStr Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
title_full_unstemmed Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli
title_sort silencing prion protein in mda-mb-435 breast cancer cells leads to pleiotropic cellular responses to cytotoxic stimuli
description Prion protein (PrP) is well studied for its pathogenic role in prion disease, but its potential contribution to other pathological processes is less understood. PrP is expressed in a variety of cancers and at least in pancreatic and breast cancers, its expression appears to be associated with poor prognosis. To understand the role of PrP in breast cancer cells, we knocked down PrP expression in MDA-MB-435 breast cancer cells with small interfering RNA and subjected these cells to a series of analyses. We found that PrP knockdown in these cells does not affect cell proliferation or colony formation, but significantly influences the cellular response to cytotoxic stimuli. Compared to control cells, PrP knockdown cells exhibited an increased susceptibility to serum deprivation induced apoptosis, no change to staurosporine- or paclitaxel-induced cell deaths, and a reduced susceptibility to chemotherapy drug doxorubicin-induced cell death. To understand the mechanism of unexpected role of PrP in exacerbating doxorubicin-induced cytotoxicity, we analyzed cell death related Bcl-2 family proteins. We found that PrP knockdown alters the expression of several Bcl-2 family proteins, correlating with increased resistance to doxorubicin-induced cytotoxicity. Moreover, the enhanced doxorubicin resistance is independent of DNA damage related p53 pathway, but at least partially through the ERK1/2 pathway. Together, our study revealed that silencing PrP in MDA-MB-435 breast cancer cells results in very different responses to various cytotoxic stimuli and ERK1/2 signaling pathway is involved in PrP silencing caused resistance to doxorubicin.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487893/
_version_ 1611920992670580736

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