Relationship between abnormal p53 protein and failure to express p21 protein in human breast carcinomas.

ABSTRACT

Alterations in the p53 protein are a common feature in most malignancies, including breast carcinomas. p53 protein alterations contribute to malignant transformation in several ways, through genomic instability and accumulation of additional genetic alterations in other genes, through alteration of the p53-dependent apoptotic pathway, and through downregulation of downstream effector proteins such as p21 (WAF1/CIP1), necessary for cell-cycle growth arrest. Cell-cycle arrest is needed to allow DNA repair after injury. This study examines the relationship between abnormalities in p53 protein and expression of p21 protein in 70 cases selected from a series of 212 sporadic human breast carcinomas. Immunohistochemistry (IHC) was used for detection of p53 and p21 protein expression. Constant denaturant gel electrophoresis (CDGE) was used for detection of mutations in exons 5-8 of the TP53 gene. A highly significant association was found between abnormalities in p53, scored as protein accumulation and/or mutations, and lack of p21 expression. p21 was also shown to be downregulated in samples without p53 alterations, indicating that other mechanisms are also involved in turning off this gene.