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01-04-2015 | Preclinical Study

The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells

Authors: Wei Bin Fang, Min Yao, Iman Jokar, Nabil Alhakamy, Cory Berkland, Jin Chen, Dana Brantley-Sieders, Nikki Cheng

Published in: Breast Cancer Research and Treatment | Issue 2/2015

Abstract

Luminal A and B breast cancers are the most prevalent forms of breast cancer diagnosed in women. Compared to luminal A breast cancer patients, patients with luminal B breast cancers experience increased disease recurrence and lower overall survival. The mechanisms that regulate the luminal B subtype remain poorly understood. The chemokine CCL2 is overexpressed in breast cancer, correlating with poor patient prognosis. The purpose of this study was to determine the role of CCL2 expression in luminal B breast cancer cells. Breast tissues, MMTV-PyVmT and MMTV-Neu transgenic mammary tumors forming luminal B-like lesions, were immunostained for CCL2 expression. To determine the role of CCL2 in breast cancer cells, CCL2 gene expression was silenced in mammary tumor tissues and cells using TAT cell-penetrating peptides non-covalently cross linked to siRNAs (Ca-TAT/siRNA). CCL2 expression was examined by ELISA and flow cytometry. Cell growth and survival were analyzed by flow cytometry, immunocytochemistry, and fluorescence microscopy. CCL2 expression was significantly increased in luminal B breast tumors, MMTV- PyVmT and MMTV-Neu mammary tumors, compared or normal breast tissue or luminal A breast tumors. Ca-TAT delivery of CCL2 siRNAs significantly reduced CCL2 expression in PyVmT mammary tumors, and decreased cell proliferation and survival. CCL2 gene silencing in PyVmT carcinoma cells or BT474 luminal B breast cancer cells decreased cell growth and viability associated with increased necrosis and autophagy. CCL2 expression is overexpressed in luminal B breast cancer cells and is important for regulating cell growth and survival by inhibiting necrosis and autophagy.

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Title: The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells
Authors: Wei Bin Fang
Min Yao
Iman Jokar
Nabil Alhakamy
Cory Berkland
Jin Chen
Dana Brantley-Sieders
Nikki Cheng
Publication date: 01-04-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3324-4

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