Expression of Novel Steroid/Receptors in Mammary Development: Peroxisome Proliferator Activated Receptors

摘要

This IDEA grant tested our hypothesis that peroxisome proliferator- activated receptor (PPAR) are expressed in the mammary gland and regulated during physiologic and pathologic events. The PPARs are nuclear hormone receptors which bind to fatty acids as ligands and control transcription of lipid metabolic genes. Due to the link between dietary fat, obesity, and breast cancer, we postulated that PPARs are potential targets for chemoprevention or chemotherapy. Based on northern blot analyses, we determined that virgin murine mammary glands express mRNA for PPARs alpha, beta, and gamma. During pregnancy and lactation, the levels of PPARs alpha and gamma decreased. Levels of PPAR gamma mRNA were below detection in rodent mammary tumors. Using a rat model of mammary tumorigenesis, we found that synthetic PPAR ligands did not inhibit tumor formation. However, these agents appeared to stimulate regression of established tumors. Additional studies will be required to establish statistical significance to this work.