2007•Journal of Toxicologic PathologyOpen access

Absence of Epidermal Growth Factor Receptor Gene Mutations in Lung and Liver Tumors in Rats

Mariko Onishi, Kyoko Shimizu, Eriko Sugata, Mayumi Fujii, Midori Yoshida, Kanya Honoki, Toshifumi Tsujiuchi

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Abstract

Epidermal growth factor receptor (EGFR), a receptor protein tyrosine kinase, is a transmembrane protein. Recent studies indicate that mutations in the gene encoding EGFR are present in several human cancers. To assess the involvement of these mutations in the development of rat tumors, we looked for the presence of mutations in exons 18-21, a region which encodes the tyrosine kinase domain of Egfr, in lung and liver tumors in rats. Lung adenocarcinomas were induced in rats by exposure to N-nitrosobis(2-hydroxypropyl)amine (BHP). We also induced hepatocellular carcinomas (HCCs) in rats with multiple hepatocarcinogens and a choline-deficient L-amino acid-defined (CDAA) diet. Genomic DNA was extracted from 12 lung adenocarcinomas, 8 HCCs induced by multiple hepatocarcinogens and 8 HCCs induced by the CDAA diet. To identify mutations in Egfr, polymerase chain reaction (PCR)- single-strand conformation polymorphism (SSCP) analysis was performed. No mutations were detected throughout exons 18-21, in either lung or liver tumors in rats. These results suggest that alterations to Egfr might not be involved in the development of lung and liver tumors in rats.

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Epidermal growth factor receptor (EGFR), a receptor protein tyrosine kinase, is a transmembrane protein. Recent studies indicate that mutations in the gene encoding EGFR are present in several human cancers. To assess the involvement of these mutations in the development of rat tumors, we looked for the presence of mutations in exons 18-21, a region which encodes the tyrosine kinase domain of Egfr, in lung and liver tumors in rats. Lung adenocarcinomas were induced in rats by exposure to N-nitrosobis(2-hydroxypropyl)amine (BHP). We also induced hepatocellular carcinomas (HCCs) in rats with multiple hepatocarcinogens and a choline-deficient L-amino acid-defined (CDAA) diet. Genomic DNA was extracted from 12 lung adenocarcinomas, 8 HCCs induced by multiple hepatocarcinogens and 8 HCCs induced by the CDAA diet. To identify mutations in Egfr, polymerase chain reaction (PCR)- single-strand conformation polymorphism (SSCP) analysis was performed. No mutations were detected throughout exons 18-21, in either lung or liver tumors in rats. These results suggest that alterations to Egfr might not be involved in the development of lung and liver tumors in rats.

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Available abstract

Epidermal growth factor receptor (EGFR), a receptor protein tyrosine kinase, is a transmembrane protein. Recent studies indicate that mutations in the gene encoding EGFR are present in several human cancers. To assess the involvement of these mutations in the development of rat tumors, we looked for the presence of mutations in exons 18-21, a region which encodes the tyrosine kinase domain of Egfr, in lung and liver tumors in rats. Lung adenocarcinomas were induced in rats by exposure to N-nitrosobis(2-hydroxypropyl)amine (BHP). We also induced hepatocellular carcinomas (HCCs) in rats with multiple hepatocarcinogens and a choline-deficient L-amino acid-defined (CDAA) diet. Genomic DNA was extracted from 12 lung adenocarcinomas, 8 HCCs induced by multiple hepatocarcinogens and 8 HCCs induced by the CDAA diet. To identify mutations in Egfr, polymerase chain reaction (PCR)- single-strand conformation polymorphism (SSCP) analysis was performed. No mutations were detected throughout exons 18-21, in either lung or liver tumors in rats. These results suggest that alterations to Egfr might not be involved in the development of lung and liver tumors in rats.

Key concepts: HCCS, Epidermal growth factor receptor, Exon, Biology, Lung cancer, Cancer research, Epidermal growth factor, Tyrosine kinase

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