| First Author | Venkatachalam S | Year | 1998 |
| Journal | EMBO J | Volume | 17 |
| Issue | 16 | Pages | 4657-67 |
| PubMed ID | 9707425 | Mgi Jnum | J:49422 |
| Mgi Id | MGI:1277467 | Doi | 10.1093/emboj/17.16.4657 |
| Citation | Venkatachalam S, et al. (1998) Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J 17(16):4657-67 |
| abstractText | Tumor suppressor genes are generally viewed as being recessive at the cellular level, so that mutation or loss of both tumor suppressor alleles is a prerequisite for tumor formation. The tumor suppressor gene, p53, is mutated in similar to 50% of human sporadic cancers and in an inherited cancer predisposition (Li-Fraumeni syndrome). We have analyzed the status of the wildtype p53 allele in tumors taken from p53-deficient heterozygous (p53+/-) mice. These mice inherit a single null p53 allele and develop tumors much earlier than those mice with two functional copies of wildtype p53, We present evidence that a high proportion of the tumors from the p53 +/- mice retain an intact, functional, wild-type p53 allele, Unlike p53 +/- tumors which lose their wild-type allele, the tumors which retain an intact p53 allele express p53 protein that induces apoptosis following gamma- irradiation, activates p21(WAF1/CIP1) and Mdm2 expression, represses PCNA expression (a negatively regulated target of wild-type p53), shows high levels of binding to oligonucleotides containing a wild-type p53 response element and prevents chromosomal instability as measured by comparative genomic hybridization. These results indicate that loss of both p53 alleles is not a prerequisite for tumor formation and that mere reduction in p53 levels may be sufficient to promote tumorigenesis. |
