Ki-ras and p53 mutations are early and late events, respectively, in urethane-induced pulmonary carcinogenesis in A/J mice
Horio, Y; Chen, A; Rice, P; Roth, JA; Malkinson, AM; Schrump, DS
| HERO ID | 1597257 |
|---|---|
| In Press | No |
| Year | 1996 |
| Title | Ki-ras and p53 mutations are early and late events, respectively, in urethane-induced pulmonary carcinogenesis in A/J mice |
| Authors | Horio, Y; Chen, A; Rice, P; Roth, JA; Malkinson, AM; Schrump, DS |
| Journal | Molecular Carcinogenesis |
| Volume | 17 |
| Issue | 4 |
| Page Numbers | 217-223 |
| Abstract | In the A/J strain of mice, urethane (ethyl carbamate) induces lung hyperplasia, adenoma, and adenocarcinoma in a time-dependent manner. These distinct morphological stages may correlate with sequential molecular genetic changes in this mouse model. To test this hypothesis, we investigated the presence of mutations involving Ki-ras and p53 in urethane-induced lung lesions in A/J mice at early and late stages of tumorigenesis. We precisely microdissected 40 lung lesions from paraffin-embedded sections. Ki-ras mutations around codon 61 and p53 mutations in exons 5-8 were identified by polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing techniques. In 29 early-stage lung lesions classified as hyperplasias (seven) or adenomas (22), we observed 19 Ki-ras mutations (66%), including three silent mutations and one double mutation at different codons, and one silent p53 mutation (3.5%). In 11 late-stage adenomas, we identified nine activating Ki-ras mutations (82%) and four missense p53 mutations (36%). These results indicate that Ki-ras mutations arise early, whereas p53 mutations occur relatively late during the benign stages of urethane-induced lung carcinogenesis in A/J mice. |
| Doi | 10.1002/(SICI)1098-2744(199612)17:4<217::AID-MC5>3.0.CO;2-A |
| Pmid | 8989915 |
| Wosid | WOS:A1996WA01800006 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030453289&doi=10.1002%2f%28SICI%291098-2744%28199612%2917%3a4%3c217%3a%3aAID-MC5%3e3.0.CO%3b2-A&partnerID=40&md5=7a0ecee08803e271335d0e6e46197344 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Ki-ras; p53; preneoplasia; tumor progression; A/J mouse |