Breast cancer is the most common cancer and the second leading cause of cancer-related deaths in women of Australia. p53 is an important tumour suppressor gene responsible for maintaining genomic stability by mediating pathways of cell cycle arrest and apoptosis in response to DNA damage. p53 is also the most highly mutated gene in human cancers. However, p53 is mutated in only ~30% of breast cancers, suggesting that other mechanisms are responsible for the loss of p53 function in breast cancer.
Recently, it was discovered that the p53 transcript gives rise to a number of p53 isoforms. These isoforms have been shown to be expressed at both the mRNA and protein level, and can regulate full length p53-mediated function. However, quantitative analysis of p53 isoform expression has yet to be examined in breast cancer. The aim of this study was to determine if p53 isoform expression is altered in human breast tissue, compared to normal adjacent tissue, and to determine if the p53 isoforms are associated with clinical pathological features of breast cancer.
In this study, the mRNA expression of p53 isoforms was examined in a cohort of 38 Grade I, 38 Grade II and 71 Grade III invasive ductal carcinomas (IDC), and 33 matched normal adjacent tissues using real-time PCR. We found that Δ40p53 was the highest expressed isoform in breast cancer, and that it was overexpressed in the tumour tissue when compared to matched normal adjacent tissue. There was no association found between isoform expression and tumour grade or lymph node status. However, Δ40p53 was associated with an aggressive subtype of breast cancer. These results suggest that Δ40p53 is differentially expressed in breast cancer and its association with an aggressive tumour subtype implies its potential use as a prognostic marker.