AGR3 promotes estrogen receptor‑positive breast cancer cell proliferation in an estrogen‑dependent manner

Jian,Lei; Xie,Jian; Guo,Shipeng; Yu,Haochen; Chen,Rui; Tao,Kai; Yang,Chengcheng; Li,Kang; Liu,Shengchun

doi:10.3892/ol.2020.11683

AGR3 promotes estrogen receptor‑positive breast cancer cell proliferation in an estrogen‑dependent manner

Authors:
- Lei Jian
- Jian Xie
- Shipeng Guo
- Haochen Yu
- Rui Chen
- Kai Tao
- Chengcheng Yang
- Kang Li
- Shengchun Liu
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Affiliations: Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of General Surgery, Yong Chuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China, The Second Department of Gynecologic Oncology, Shaanxi Provincial Tumor Hospital, The Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 28, 2020 https://doi.org/10.3892/ol.2020.11683
Pages: 1441-1451
Copyright: © Jian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the most common malignancies and the leading cause of cancer‑associated death among women. Anterior gradient 3 (AGR3) is a cancer‑associated gene and is similar to its homologous oncogene AGR2. However, whether AGR3 participates in breast cancer progression remains unclear. The present study aimed to investigate the function of AGR3 in ER‑positive breast cancer. In the present study, reverse transcription‑quantitative PCR was used to detect AGR3 mRNA expression in breast cancer tissues and cell lines; linear correlation analysis was used to investigate the correlation between AGR3 and estrogen receptor 1 (ESR1) expression in breast cancer via GEO dataset analysis; western blotting was used to assess the levels of AGR3, ER and GAPDH; small interfering (si)RNA transfection was used to knock down AGR3 and ESR1 expression; and finally the Cell Counting Kit‑8 assay was used to evaluate cell viability. In the present study, AGR3 expression was markedly increased in estrogen receptor (ER)‑positive breast cancer tissues and cell lines compared with that in ER‑negative breast cancer. AGR3 expression was upregulated in estrogen‑treated T47D cells, whereas 4‑hydroxytamoxifen, an inhibitor of estrogen‑ER activity in breast cancer cells, downregulated AGR3 expression in T47D cells. Functional assays demonstrated that knockdown of AGR3 using siRNAs inhibited T47D cell proliferation compared with that of the negative control group. Additionally, AGR3 expression was decreased after knocking down ESR1. The present results suggested that AGR3 may serve an important role in estrogen‑mediated cell proliferation in breast cancer and that AGR3 knockdown may be a potential therapeutic strategy for ER‑positive breast cancer.

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