Characterization of peroxisome proliferator-activated receptor alpha in normal rat mammary gland and 2-amino-l-methyl-6-phenylimidazo[4, 5-b]pyridine-induced mammary gland tumors from rats fed high and low fat diets.
Normal Sprague-Dawley rat mammary gland epithelial cells and mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine, a carcinogen found in the diet, were examined for the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha). PPAR alpha mRNA and protein was detected in normal and tumor tissue by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. By quantitative RT-PCR, carcinomas had a 12-fold higher expression than control mammary glands, a statistically significant difference. PPAR alpha expression was examined in carcinomas and normal tissues from rats on high fat (23.5% corn oil) and low fat (5% corn oil) diets. Although neither carcinomas, nor control tissues showed statistically significant differences between the two diet groups, PPAR alpha expression was the highest in carcinomas from rats on the high fat diet. The expression of PPAR alpha in normal mammary gland and its significant elevation in mammary gland carcinomas raises the possibility of its involvement in mammary gland physiology and pathophysiology.
Roberts-Thomson
S J
SJ
School of Pharmacy, The University of Queensland, St. Lucia, Qld 4072, Australia. s.roberts-thompson@pharmacy.uq.edu.au
Snyderwine
E G
EG
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D007093:Imidazoles / Q000633:toxicity*; D007150:Immunohistochemistry; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D002273:Carcinogens; D004041:Dietary Fats; D007093:Imidazoles; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine