Estrogen receptor β inhibits breast cancer migration and promotes its apoptosis through NF-κB/IL-8 signaling.

Abstract

Background: Estrogen receptor β (ERβ) has been confirmed to play a tumor suppressor effect in various cancers, but its role in breast cancer is still unclear, especially in triple-negative breast cancer. In this study, we aim to explore the expression of ERβ in breast cancer and its influence on the biological behavior of breast cancer cells, including its potential mechanisms of action.

Methods: MCF-7 and MDA-MB-231 breast cancer cell lines were transfected with ERβ-overexpressing lentivirus and treated with pyrrolidinedithiocarbamate ammonium, a specific inhibitor of NF-κB. Cell Counting Kit-8, colony formation, and apoptosis assays were used to examine breast cancer cells viability in vitro. We further investigated breast cancer cells mobility and migration through wound healing and transwell assays. Western blot and quantitative real-time polymerase chain reaction analysis determined the expression of related genes at the protein and messenger RNA levels.

Results: Breast cancer tissues displayed significantly lower ERβ messenger RNA and protein levels compared to adjacent healthy tissues. Conversely, interleukin-8 (IL-8) messenger RNA and protein levels were significantly higher in cancer tissues. ERβ overexpression led to a reduction in the expression of NF-κB pathway proteins like p-IκBα and p-P65, thereby inhibiting the pathway and consequently decreasing the expression of the inflammatory factor IL-8. This resulted in decreased mobility and migration of breast cancer cells, accompanied by increased apoptosis.

Conclusions: This study demonstrates that ERβ suppresses the NF-κB/IL-8 signaling axis by inhibiting the phosphorylation of IκBα and P65, consequently restricting breast cancer cell mobility and migration while promoting apoptosis.