Expression of PPAR-alpha and gamma in breast cancer patients and their relationship with the expression of FASN, ACSL4, and ACLY genes.

BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptors alpha and gamma (PPAR-α and PPAR-γ) are nuclear receptor proteins that play a crucial role in the regulation of cellular differentiation, development, metabolism, and tumorigenesis. Their expression levels have been implicated in the metabolic reprogramming of breast cancer cells, influencing their proliferation and survival. This study investigates the expression of PPAR-α and PPAR-γ in breast cancer and explores their relationship with key enzymes involved in fatty acid biosynthesis: fatty acid synthase (FASN), acyl-CoA synthetase long-chain family member (ACSL4), and ATP citrate lyase (ACLY). EXPERIMENTAL APPROACH: In this study, 28 pairs of fresh samples of breast cancer and adjacent non-cancerous tissue were analyzed to assess gene expression levels using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. FINDINGS/RESULTS: The expression of PPAR-α increased, while PPAR-γ decreased significantly in breast cancer tissues compared to adjacent normal tissues. The expression of PPAR-α was significantly associated with FASN mRNA expression. Additionally, a correlation was also observed between the expression levels of both PPAR-α and PPAR-γ with ACSL4 mRNA levels. CONCLUSION AND IMPLICATIONS: Given the obtained results, the involvement of PPARs in the regulation of lipid metabolism was substantiated. Moreover, the correlation of PPARs with ACSL4 highlights the possible role of PPAR-α and PPAR-γ in the regulation of tumor tissue ferroptosis and suggests that targeting these pathways could offer new therapeutic strategies for managing breast cancer. However, further studies are needed to understand the mechanism of action.