Rui Jiang1, Yongjie Sun2, Xiao Chen3, Peng Shi4. 1. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwuweiqi Road, Huaiyin District, Jinan, 250000, China. 2. Department of Breast and Thyroid Diseases, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, No. 4 Duanxing West Road, Huaiyin District, Jinan, 250000, China. 3. Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwuweiqi Road, Huaiyin District, Jinan, 250000, China. 4. Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwuweiqi Road, Huaiyin District, Jinan, 250000, China. ship1998@163.com.
Abstract
PURPOSE: Anterior gradient 3 (AGR3) is associated with breast cancer progression, but its relationship with estrogen and tamoxifen resistance in breast cancer is still unclear. This study was designed to investigate the correlation of ARG3 and estrogen as well as the roles of ARG3 in tamoxifen resistance in breast cancer. METHODS: Online database including GEPIA, UALCAN, and TCGA and rVista predictive tool were applied to analyze the expression patterns of AGR3 and its relationship with estrogen receptor 1. AGR3 knockdown and overexpression cell models were constructed. Luciferase reporter assay and ChIP were performed to investigate intermolecular interactions. Western blotting and qPCR were applied to assess targets at mRNA and protein levels, respectively. Cell counting and MTT assay were applied to determine the cell proliferation. RESULTS: An elevation of AGR3 was observed in patients with breast cancer, especially in the patients with estrogen receptor (ER)-positive breast cancer. The TCGA dataset and in vitro data supported that AGR3 was positively correlated to ER. Further results demonstrated that ER protein bound to AGR3 promoter sites. AGR3 expression exhibited a positive correlation to cell viability. Besides, AGR3 promoted tamoxifen resistance in breast cancer. CONCLUSION: AGR3 is associated with estrogen and promotes tamoxifen resistance in breast cancer.
PURPOSE: Anterior gradient 3 (AGR3) is associated with breast cancer progression, but its relationship with estrogen and tamoxifen resistance in breast cancer is still unclear. This study was designed to investigate the correlation of ARG3 and estrogen as well as the roles of ARG3 in tamoxifen resistance in breast cancer. METHODS: Online database including GEPIA, UALCAN, and TCGA and rVista predictive tool were applied to analyze the expression patterns of AGR3 and its relationship with estrogen receptor 1. AGR3 knockdown and overexpression cell models were constructed. Luciferase reporter assay and ChIP were performed to investigate intermolecular interactions. Western blotting and qPCR were applied to assess targets at mRNA and protein levels, respectively. Cell counting and MTT assay were applied to determine the cell proliferation. RESULTS: An elevation of AGR3 was observed in patients with breast cancer, especially in the patients with estrogen receptor (ER)-positive breast cancer. The TCGA dataset and in vitro data supported that AGR3 was positively correlated to ER. Further results demonstrated that ER protein bound to AGR3 promoter sites. AGR3 expression exhibited a positive correlation to cell viability. Besides, AGR3 promoted tamoxifen resistance in breast cancer. CONCLUSION: AGR3 is associated with estrogen and promotes tamoxifen resistance in breast cancer.
Authors: Wanjing Shang; Yong Jiang; Michael Boettcher; Kang Ding; Marianne Mollenauer; Zhongyi Liu; Xiaofeng Wen; Chang Liu; Piliang Hao; Suwen Zhao; Michael T McManus; Lai Wei; Arthur Weiss; Haopeng Wang Journal: Proc Natl Acad Sci U S A Date: 2018-04-09 Impact factor: 11.205