title: Tamoxifen has a proliferative effect in endometrial carcinoma mediated via the GPER/EGFR/ERK/cyclin D1 pathway: A retrospective study and an in vitro study.
abstract: Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. However, tamoxifen is known to enhance the risk of developing endometrial cancer. We want to examine the effect of tamoxifen on endometrial cancer. In our retrospective study, we found that high grade, high stage, and lymph node metastasis were more common in tamoxifen users. In vitro 4-hydroxytamoxifen (OHT) induced cell proliferation and cell cycle promotion in type I and type II endometrial cancer cell lines, and this proliferation was blocked by GPER silencing. Treatment with OHT increased EGFR and ERK phosphorylation and the mRNA and protein levels of cyclin D1 and GPER. Taken together, our data demonstrate that endometrial cancer patients with tamoxifen treatment exhibit more aggressive histological subtypes and worse prognosis. OHT is a proliferation-inducing agent for endometrial cancer cells, and the GPER/EFGR/ERK/cyclin D1 pathway is involved in this process.
authors: Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin, 300192, China. Electronic address: zhlizh1234@163.com.
authors: Lizhi
authors: L
authors: Zhang
authors: Department of Pathology, Tianjin First Center Hospital, Tianjin, 300192, China. Electronic address: tjslym@sina.com.
authors: Yanmin
authors: Y
authors: Li
authors: Department of Synergistic Chinese and Western Medicine Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. Electronic address: lanlan9427@126.com.
authors: Lan
authors: L
authors: Lan
authors: Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin, 300192, China. Electronic address: liuronghch1999@sina.com.
authors: Rong
authors: R
authors: Liu
authors: Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin, 300192, China. Electronic address: wyh650118@163.com.
authors: Yanhong
authors: Y
authors: Wu
authors: Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin, 300192, China. Electronic address: qqxin95425@126.com.
authors: Quanxin
authors: Q
authors: Qu
authors: Department of Pharmacology, Tianjin Medical University, Tianjin, 300070, China. Electronic address: kewencn@163.com.
authors: Ke
authors: K
authors: Wen
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: C109584:GPER1 protein, human; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D013629:Tamoxifen; D019938:Cyclin D1; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cell cycle; Endometrial cancer; Prognosis; Proliferation; Signaling pathway; Tamoxifen