# Estrogen-Dependent Regulation of FDPS in the Mouse Uterus and Its Expression in Endometrial Cancer

## TL;DR

Estrogen regulates FDPS in the mouse uterus, and high FDPS levels are found in endometrial cancer, suggesting it could be a new treatment target.

## Contribution

This study reveals estrogen-dependent regulation of FDPS and its potential role in endometrial cancer progression.

## Key findings

- FDPS expression in the mouse uterus is regulated by estrogen, peaking during the proestrus stage.
- FDPS is highly expressed in human endometrial cancer tissues and promotes cancer cell proliferation.
- Estrogen receptor alpha mediates FDPS regulation, as shown by ERα antagonist effects in mice.

## Abstract

The uterus is a dynamic organ in which the endometrium undergoes cyclic processes of proliferation, shedding, and regeneration under the influence of estrogen and progesterone. In particular, estrogen regulates the proliferation and differentiation of the endometrium and plays an important role in the development of gynecological diseases such as endometrial cancer. Farnesyl diphosphate synthase (FDPS) is a key enzyme involved in the mevalonate pathway, catalyzing the synthesis of farnesyl pyrophosphate (FPP), which plays an essential role in cholesterol biosynthesis and protein prenylation. In this study, we demonstrated using an in vivo mouse model that the expression of FDPS is regulated by estrogen. FDPS expression was specifically elevated during the proestrus stage of the estrous cycle and subsequently decreased. In ovariectomized (OVX) mice, FDPS expression was significantly increased 24 h after estrogen treatment, whereas this response was suppressed by treatment with the estrogen receptor alpha (ERα) antagonist, ICI 182,780. Although FDPS expression has been reported in various cancers, its role in endometrial cancer remains unclear. Histological and cellular analyses revealed that FDPS is highly expressed in human endometrial cancer tissues and in the endometrial cancer cell line Ishikawa, where it contributes to cell proliferation. These findings suggest that FDPS may play a role in the survival and growth of endometrial cancer cells. This study provides new insights into the potential function of FDPS in the uterus and suggests that targeting FDPS may represent a promising therapeutic strategy for endometrial cancer.