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
M W
MW
Greenville Hospital/Clemson University Cooperative Research and Education Program, Clemson University, SC 29634-2001, USA. MKilgor@Clemson.Edu
Tate
P L
PL
Rai
S
S
Sengoku
E
E
Price
T M
TM
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors