ANALYSIS OF EGFR, TGF-ALPHA, NEU AND C-MYC IN NO-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 foun d in cooked meat, has been shown to induce mammary gland tumors in rat s, Our laboratory recently observed that a high fat diet enhances the incidence and severity of PhIP-induced mammary gland cancer in rats. I n the current study, reverse transcription followed by polymerase chai n reaction amplification was used to determine whether EGFR, TGF-alpha , neu and c-myc are differentially expressed in PhIP-induced mammary g land tumors classified histologically as benign or malignant and to ev aluate whether dietary fat intake influences the expression of these g enes, Of 23 total PhIP-induced mammary tumors examined, 43%, 57% and 7 4% had increased expression of EGFR, TGP-alpha and neu mRNA respective ly, Increased expression of these genes appeared to be consistently pr esent in tumors displaying papillomatosis. In contrast to the other th ree genes, c-myc mRNA levels were infrequently elevated. The percentag e of dietary fat did not appear to influence the expression of EGFR, T GF-alpha or neu in either tumors or mammary gland from control rats, H owever, 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 r ats fed the high-fat diet than in rats fed the low-fat diet, suggestin g a slight effect of dietary fat (P < 0.08) on c-myc expression. These results suggest that increased expression of EGFR, TGF-alpha and espe cially neu is associated with PhIP-induced mammary gland cancer in rat s.