G-Protein-coupled Estrogen Receptor 1 (GPER1) Overexpression Affects Aggressiveness of Cervical Carcinoma Cells Depending on Histological Entity.

Background/aim: Cervical cancer (CC) is the fourth most common cancer in women worldwide. There are two main histological subtypes of CC: the more common cervical squamous cell carcinoma (CSCC) and the rarer cervical adenocarcinoma (CAC), which has a poorer prognosis. Unlike estrogen receptor (ER) α and ERβ, G-protein-coupled estrogen receptor 1 (GPER1) is recognized as a rapid mediator of cellular estrogenic action and tends to have tumor suppressive properties in CC. Since a clinical study showed that an elevated GPER1 expression is associated with a worse prognosis, we investigated the effects of stable GPER1 overexpression (GPER1-OE) on SiHa CSCC and HeLa CAC cells.

Materials and methods: SiHa CSCC and HeLa CAC cells with stable GPER1-OE were generated. GPER1-OE was tested by RT-qPCR, western blot and fluorescence-activated cell analysis (FACS). The effects of GPER1-OE on proliferation, migration, invasion, apoptosis and stem cell properties (colony and sphere formation) were then examined.

Results: Successful GPER1-OE in SiHa CSCC and HeLa CAC cells was confirmed. The cell characterization experiments showed that SiHa CSCC cells with stable GPER1-OE had faster proliferation and migration, and increased stem cell properties with larger and more numerous colonies and larger tumor spheres. In HeLa CAC cells, on the other hand, GPER1-OE resulted in slower cell proliferation, migration and invasion, reduced colony formation and tumor sphere formation. An increased rate of apoptosis was also observed.

Conclusion: GPER1-OE resulted in a more aggressive tumor behavior of SiHa CSCC cells and a less aggressive tumor behavior of HeLa CAC cells, due to a different effect of GPER1 overexpression depending on the respective histological subtypes of CC. This underlines the need for personalized medicine and a precise differentiation of subtypes in CC-related research.