Inhibition of proliferation of estrogen receptor‑positive MCF‑7 human breast cancer cells by tamoxifen through c‑Jun transcription factors

Xu,Yan; Zou,Shi‑Tao; Zhu,Ran; Li,Wei; Gu,Chun‑Wei; Wei,Shao‑Hua; Xie,Jia‑Ming; Wu,Hao‑Rong

doi:10.3892/mmr.2013.1306

Inhibition of proliferation of estrogen receptor‑positive MCF‑7 human breast cancer cells by tamoxifen through c‑Jun transcription factors

Authors:
- Yan Xu
- Shi‑Tao Zou
- Ran Zhu
- Wei Li
- Chun‑Wei Gu
- Shao‑Hua Wei
- Jia‑Ming Xie
- Hao‑Rong Wu
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Affiliations: Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R China, Institute of Cancer Research, Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China, School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: February 5, 2013 https://doi.org/10.3892/mmr.2013.1306
Pages: 1283-1287

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Abstract

Activator of protein 1 (AP‑1) is a heterodimeric transcription factor composed of various members of the Jun and Fos families and binds to DNA at specific AP‑1 binding sites. AP‑1 transcriptional activity is increased by phosphorylation at serine residues in the c‑Jun component of AP‑1. In the present study, the proliferation of MCF‑7 breast cancer cells was found to be suppressed by tamoxifen (TAM)‑activated c‑Jun through the protein kinase C (PKC) pathway. The molecular mechanism by which c‑Jun activation induces antiproliferative signals in estrogen receptor (ER)‑positive MCF‑7 human breast cancer cells remains unknown. TAM inhibited the proliferation of ER‑positive MCF‑7 human breast cancer cells and ER‑negative MDA‑MB‑435 human breast cancer cells and 48 h incubation with 10 µM TAM led to inhibition of 80% of proliferation. In addition, no significant difference in c‑Jun mRNA and protein levels was detected in MCF‑7 and MDA‑MB‑435 cells stimulated by TAM for 48 h. TAM treatment of MCF‑7 cells activated the transcriptional activity of AP‑1, which responds specifically to phorbol ester. To determine the role of c‑Jun in the antiproliferation of MCF‑7 cells stimulated by TAM, the inhibition rates of MCF‑7 cells were correlated with c‑Jun expression and stimulation of TAM. Results showed that the inhibition rate of TAM‑stimulated MCF‑7 cells was positively regulated by overexpression of c‑Jun and negatively regulated by underexpression of c‑Jun. Overall, these results indicate that the TAM‑stimulated antiproliferation of MCF‑7 cells is positively regulated by c‑Jun through activation of the PKC pathway.

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