Analysis of EGFR, TGF-alpha, neu and c-myc in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary tumors using RT-PCR.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a mutagen found in cooked meat, has been shown to induce mammary gland tumors in rats. Our laboratory recently observed that a high fat diet enhances the incidence and severity of PhIP-induced mammary gland cancer in rats. In the current study, reverse transcription followed by polymerase chain reaction amplification was used to determine whether EGFR, TGF-alpha, neu and c-myc are differentially expressed in PhIP-induced mammary gland tumors classified histologically as benign or malignant and to evaluate whether dietary fat intake influences the expression of these genes. Of 23 total PhIP-induced mammary tumors examined, 43%, 57% and 74% had increased expression of EGFR, TGF-alpha and neu mRNA respectively. Increased expression of these genes appeared to be consistently present in tumors displaying papillomatosis. In contrast, to the other three genes, c-myc mRNA levels were infrequently elevated. The percentage of dietary fat did not appear to influence the expression of EGFR, TGF-alpha or neu in either tumors or mammary gland from control rats. However, the levels of c-myc mRNA were 1.8- and 2.9-fold higher in the control mammary gland and benign PhIP-induced tumors respectively in rats fed the high-fat diet than in rats fed the low-fat diet, suggesting a slight effect of dietary fat (P < 0.08) on c-myc expression. These results suggest that increased expression of EGFR, TGF-alpha and especially neu is associated with PhIP-induced mammary gland cancer in rats.
Davis
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Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Snyderwine
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D016259:Genes, myc; D007093:Imidazoles / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000235:genetics
D002273:Carcinogens; D017931:DNA Primers; D004041:Dietary Fats; D007093:Imidazoles; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine