Analysis of the c-myc, K-ras and p53 Genes in Methylcholanthrene induced Mouse Sarcomas |
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Authors: | Hiroshi Watanabe Kiyoshi Shimokado Toshimasa Asahara Kiyohiko Dohi Ohtsura Niwa |
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Affiliation: | Second Department of Surgery, Hiroshima University School of Medicine, Kasumi, Minami-ku, Hiroshima 734–0001 and;Radiation Biology Center, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606–000 |
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Abstract: | We have examined 63 methylcholanthrene (MCA)-induced mouse sarcomas for possible correlations of mutations involving the c-myc, ras and p53 genes. The c-myc gene was found to be amplified in 18 of these sarcomas (29%). Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent direct sequencing identified 18 cases carrying K-ras mutation at codons 12, 13 and 61 (29%). No mutation was detected in the H-ras and N-ras genes. Mutations of the p53 gene in exons 5 to 8 were found in 45 cases (71%). Comparison of these mutations revealed that out of 18 cases with c-myc gene amplifications, 10 carried K- ras mutations (56%) and 14 carried p53 mutations (78%). In contrast, among 45 cases of sarcomas without c-myc gene amplification, 8 were found to have K- ras mutations (18%). The same 45 cases were found to have 31 p53 mutations (69%). The present study suggests a strong correlation between c-myc gene amplification and K- ras gene mutation ( P < 0.01). p53 gene mutation was frequently found among MCA-induced mouse sarcomas, indicating the importance of this mutation in the etiology of these tumors. However, p53 mutations were present in sarcomas regardless of the state of c-myc amplification and K- ras mutation. Therefore, a defect in the p53 gene is independent of amplification of the c-myc gene or point mutation of the K- ras gene. |
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Keywords: | c-myc K-ras p53 MCA Mouse sarcoma |
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