Peroxisome proliferator-activated receptor subtypes in mammary gland development and breast cancer

Background: Peroxisome proliferator-activated receptors (PPARs) have a pivotal role in regulating genes that are involved in lipid homeostasis.Methods: We examined the mouse mammary gland during different developmental stages and assessed the relative expression of PPARs. We also examined the expression of PPARs in breast cell lines and tumors.Results: Each isoform was detected at all stages of mammary gland development but the relative profile of each isoform differed between glands from animals that were nulliparous, pregnant, lactating or involuting. PPARα and PPARγ were highest in glands from nulliparous animals, whereas PPARβ/δ was highest in glands from pregnant mice. Since many tumors are also characterized by changes in lipid profile we examined the expression of PPARs in breast cell lines and tumors. PPARα expression was higher in basal breast cancers and high expression levels were associated with reduced human breast cancer patient survival, whereas PPARγ expression did not differ between breast cancer subtypes. PPARβ/δ expression was upregulated in breast tumors of the basal and HER2 enriched breast cancer subtypes and intermediate and high levels of PPARβ/δ expression were associated with a poor outcome for breast cancer patient survival.Conclusion: These results show that the profile of PPAR isoform expression changes with mammary gland morphological and functional development and maybe important in breast tumorigenesis.