MCF-7 and T47D human breast cancer cells contain a functional peroxisomal response.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that regulate transcription of target genes. Since attempts have been made to correlate the ingestion of high-fat diets, itself a peroxisome proliferator, with the occurrence of breast cancer, we set about to determine if human breast cancer cells contained a functional PPAR. In this report we demonstrate the presence of an mRNA in two breast cancer cell lines (MCF-7 and T47D) which is specifically recognized by a mouse PPARgamma2 probe. Furthermore, in gel shift assays a consensus PPAR response element (PPRE) was specifically bound by nuclear extracts from MCF-7 cells and was further retarded by antibodies raised to mouse PPARgamma. Finally, when transfected with a PPRE-luciferase transcriptional reporter construct, transcription was increased in response to activators of PPAR and its dimmeric partner the retinoic acid X receptor (RXR). These data indicate that peroxisomal proliferators are capable of mediating transcription in human breast cells and suggest the possibility of a physiological role in the breast.
Kilgore, MW; Tate, PL; Rai, S; Sengoku, E; Price, TM
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