Ell3 stimulates 5-FU resistance in a breast cancer cell line

Kim,Isaac; Kim,Kwang‑Soo; Kwon,Ok‑Seon; Cha,Hyuk‑Jin; Park,Kyung‑Soon

doi:10.3892/ol.2017.5996

Ell3 stimulates 5-FU resistance in a breast cancer cell line

Authors:
- Isaac Kim
- Kwang‑Soo Kim
- Ok‑Seon Kwon
- Hyuk‑Jin Cha
- Kyung‑Soon Park
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Affiliations: Department of Biomedical Science, College of Life Science, CHA University, Seongnam‑si, Gyeonggi‑do 13496, Republic of Korea, Department of Life Science, College of Natural Science, Sogang University, Seoul 04107, Republic of Korea
Published online on: April 5, 2017 https://doi.org/10.3892/ol.2017.5996
Pages: 4173-4179
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ell3 is an RNA polymerase II transcription elongation factor that acts as a negative regulator of p53 expression, and regulates cell proliferation and survival. Recent studies by our group have demonstrated that ectopic expression of Ell3 in breast cancer cell lines enhances cell proliferation, potentiates cancer stem cell properties, and promotes 5-Fluorouracil (5‑FU) resistance. In the present study, the underlying mechanism for the induction of 5‑FU resistance was investigated in Ell3 over‑expressing MCF‑7 cells (Ell3 OE cells). By comparing the gene expression profiles of Ell3 OE cells with control cells, the present data revealed that Lipocalin2 (LCN2) and Wnt signaling activity are associated with 5-FU resistance of Ell3 OE. siRNA‑mediated suppression of LCN2 reversed 5‑FU resistance in Ell3 OE cells. Chemical inhibition of Wnt signaling also reversed 5‑FU resistance in Ell3 OE cells. Furthermore, the expression levels of survivin, which is a direct transcriptional target of Wnt/β‑catenin and an inhibitor of apoptosis, were markedly elevated when Ell3 OE cells were treated with 5‑FU, as detected by western blot analysis. These findings suggest that enhanced expression of LCN2 and activation of the Wnt signaling pathway may induce 5‑FU resistance in Ell3 OE cells as a means of evading apoptosis.

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