Assessment of mdm2 Alterations on p53 Expression in Breast Cancer

摘要

Mdm2 is part of a complex mechanism that regulates the expression of p53 tumor suppressor. mdm2 mRNA expression was characterized in a cohort of invasive breast cancers and normal breast specimens. Mdm2 reverse-transcription polymerase chain reaction (RT-PCR) products included full-length mdm2 (1526 bp) as well as smaller products (653, 281, 254 and 219 bp). The 653 bp product was an alternatively spliced product, while the 281, 254, and 219-bp mdm2 products were aberrantly spliced. RT-PCR with normal breast RNA samples yielded only the 1526 bp product and a small amount of the 653 bp product. The 653 bp alternatively spliced product was expressed at increased levels in 21% of breast cancers and the smaller aberrantly spliced mRNA products (281 bp, 254 bp and/or 219 bp) were expressed in another 16% of breast cancers. The alternatively spliced mRNAs and aberrantly spliced mRNAs lacked either the entire binding domain for p53 or the majority of the binding domain. An association was demonstrated between expression of aberrantly and/or alternatively spliced mdm2 mRNAs and a lack of progesterone receptor, or the presence of p53 tumor suppressor gene mutations. The presence of aberrant expression products of mdm2 in breast cancer specimens was correlated with a shortened overall patient survival.