Assessment of mdm2 Alterations on p53 Expression in Breast Cancer
Abstract
The mdm2 oncogene regulates the activity of a number of genes critical to generic integrity. mdm2 can inhibit p53 mediated transactivation as well as control the rapid degradation of p53 protein. mdm2 also inhibits retinoblastoma protein (Rb) and enhances E2Fl and DPl protein activity. The overall effect is to promote transition to S-phase. This study was undertaken to characterize mdm2 in a cohort of invasive breast cancers and to establish if there are correlations with breast cancer prognostic markers. mdm2 gene amplification was not identified in human breast carcinomas although it has been found in pediatric sarcomas. However, characterization of the mdm2 mRNA by reverse transcripts-polymer-ase chain reaction demonstrated not only the expected full- length expression product but alternatively and aberrantly spliced mRNAs as well. A full-length 1526 base-pair mdm2 mRNA was present in 97% of breast cancers analyzed. Smaller mdm2 mRNAs, measuring 653, 281, 254, and/or 219 base-pairs in length, were also identified in 30% of breast cancers. DNA sequence analysis demonstrated that the 653 base-pair mRNAs were the result of alternative splicing while the other smaller mRNAs were the result of aberrant splicing. Each of these alternatively and aberrantly spliced mRNA products was shown to lack important mdm2 functional domains.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA369306
Entities
People
- Da-quing Gao
Organizations
- University of Southern California