Chemotherapy treatment induces an increase of autophagy in the luminal breast cancer cell MCF7, but not in the triple-negative MDA-MB231

Christian Garbar,Yacine Merrouche,Armand Bensussan,Corinne Mascaux,Jérôme Giustiniani

doi:10.1038/s41598-017-07489-x

Abstract

Autophagy is one of the chemotherapy resistance mechanisms in breast cancer. The aim of this study was to determine the level of recruitment of the autophagy pathway in the triple-negative breast cancer (TNBC) cell line MDA-MB231 compared with that in the control luminal breast cancer cell line MCF7 before and after treatment with chemotherapy drugs. Furthermore, we investigated the relationship between autophagy and EGFR, MUC1 and IL17-receptors as activators of autophagy. Immunohistochemistry was performed in cell culture blocks using LC3b, MUC1-C, EGFR, IL17A, IL17-RA and IL17-RB antibodies. We found that the basal autophagy level in MDA-MB231 was high, whereas it was low in MCF7. However, in contrast to MDA-MB231, the autophagy level was increased in MCF7 upon treatment with chemotherapy agents. Interestingly, we observed that the expression levels of MUC1-C, EGFR, IL17-RA, and IL17-RB were not modified by the same treatments. Furthermore, the chemotherapy treatments did not increase autophagy in TNBC cells without affecting the expression levels of MUC1-C, EGFR, IL17-RA or IL17-RB.

Highlights

Perou’s biological and clinical classification of breast cancers (BCs) was proposed by the St Galen International Expert Consensus and is currently widely used in the clinic
Basal autophagy level is high in MDA-MB231 cells and is not influenced by chemotherapy drugs
The MDA-MD231 cell line consists of triple-negative breast cancer cells that do not express estrogen and progesterone receptors or HER2

Summary

Introduction

Perou’s biological and clinical classification of breast cancers (BCs) was proposed by the St Galen International Expert Consensus and is currently widely used in the clinic. This classification system proposes the following three main molecular subtypes: luminal (LUM) BC, which expresses hormonal estrogen and progesterone receptors (ER+ and PR+) but no human epidermal growth receptor 2 (HER2-); overexpressed HER2 BC (ER+/− PR+/− HER2+); and triple negative (TN) BC, which lacks these receptors HER2, ER and PR1, 2. Autophagy is a complex pathway involving multiple proteins. Chemotherapy resistance is due to multiple mechanisms, including autophagy. In breast cancer, epirubicin reduces autophagy and protects cells from chemotherapy-induced apoptosis. In colorectal cancer, oxaliplatin and 5-fluorouracil were found to have an improved efficiency in the presence of an anti-autophagy agent, whereas in lung cancer, anti-EGFR agents (i.e., gefitinib or erlotinib) activate autophagy and induce drug resistance[7]

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