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.

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.

Zhang L ，Li Y ，Lan L ，Liu R ，Wu Y ，Qu Q ，Wen K ... -  《-》

GPER mediates the Egr-1 expression induced by 17β-estradiol and 4-hydroxitamoxifen in breast and endometrial cancer cells.

Vivacqua A ，Romeo E ，De Marco P ，De Francesco EM ，Abonante S ，Maggiolini M ... -  《-》

Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα).

Tsai CL ，Wu HM ，Lin CY ，Lin YJ ，Chao A ，Wang TH ，Hsueh S ，Lai CH ，Wang HS ... -  《PLoS One》

Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen-resistant breast cancer cell: a new role for G protein-coupled estrogen receptor in mediating tamoxifen resistance through cancer-associated fibroblast-derived fibronectin and β1-

Yuan J ，Liu M ，Yang L ，Tu G ，Zhu Q ，Chen M ，Cheng H ，Luo H ，Fu W ，Li Z ，Yang G ... -  《-》

Cyclin D1 is necessary for tamoxifen-induced cell cycle progression in human breast cancer cells.

Kilker RL ，Planas-Silva MD 《CANCER RESEARCH》