Expression of peroxisome proliferator activated receptor mRNA in normal and tumorigenic rodent mammary glands.

The peroxisome proliferator activated receptors (PPARs) alpha, beta/delta, and gamma are novel nuclear hormone receptors activated by long chain fatty acids and synthetic ligands and which regulate lipid metabolism. Recent studies have detected PPARgamma mRNA in human mammary tumor cell lines. The current study examined the expression profile of PPAR mRNAs in normal and malignant rodent mammary tissues. Virgin murine mammary glands contained PPAR alpha, beta/delta, and gamma mRNAs based on northern blot analysis. The PPARgamma isoform was predominantly gamma2 based on quantitative PCR analysis. During pregnancy and lactation, the PPARalpha and gamma mRNAs decreased while the PPAR beta/delta mRNA remained relatively unchanged. NMuMG cells, an epithelial line derived from normal murine mammary gland, expressed PPAR alpha, beta/delta, and gamma mRNAs, independent of the presence or absence of compounds modifying PPAR activity. In rats, the physiologic expression pattern of PPARgamma mRNA paralleled the murine model; levels were detected in virgin but not lactating mammary glands. In addition, the PPARgamma mRNA was not detected in several histologically distinct 7,12-dimethylbenz(a)anthracene induced mammary tumors. These findings suggest that PPARs may regulate mammary epithelial and stromal cell function in response to physiologic or pathologic stimuli that profoundly alter lipid metabolism.

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