# Long-Chain Fatty Acids Alter Estrogen Receptor Expression in Breast Cancer Cells

## TL;DR

This study shows that certain long-chain fatty acids can change estrogen receptor levels in breast cancer cells, affecting how they respond to hormones and drugs.

## Contribution

The paper reveals novel mechanisms by which specific fatty acids modulate estrogen receptor expression in breast cancer cells through epigenetic and post-transcriptional pathways.

## Key findings

- Oleic acid reduced estrogen receptor alpha (ERα) levels in MCF7 cells, impairing estradiol and tamoxifen responses.
- Palmitic acid increased nuclear ERα in MB231 cells, though ER signaling remained inactive.
- MicroRNA profiling linked fatty acid exposure to changes in miRNA levels that regulate ERα expression.

## Abstract

Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid (EA), palmitic acid (PA), and α-linolenic acid (LNA)—on two BCA cell lines: luminal-type MCF7 and triple-negative MDA-MB-231 (MB231). All LCFAs suppressed cell viability and mitochondrial function in a dose-dependent manner, accompanied by decreased membrane potential, increased reactive oxygen species production, and a metabolic shift. Notably, OA reduced both mRNA and nuclear protein levels of estrogen receptor alpha (ERα) in MCF7 cells, leading to impaired responses to estradiol and tamoxifen. In contrast, PA induced nuclear ERα expression in MB231 cells, although ER signaling remained inactive. MicroRNA profiling revealed that OA upregulated ER-suppressive miR-22 and miR-221 in MCF7, while PA increased miR-34a in MB231, contributing to ERα induction. These findings suggest that specific LCFAs modulate ER expression through epigenetic and post-transcriptional mechanisms, altering hormonal responsiveness in BCA. Our results offer new insights into how dietary lipids may influence therapeutic efficacy and tumor behavior by regulating nuclear receptor signaling.