Most cancers can be cured by either chemotherapy and/or surgery if detected at an early stage in their development. Toward this goal of identify cancer at the earliest stage possible, we have been examining the usefulness of a unique isoform of PCNA for detecting early stage breast cancer. Our focus on PCNA stems from previous studies with a replication competent multiprotein DNA replication complex. This complex was shown by us to be the cellular DNA synthetic apparatus and it was given the name, DNA synthesome, by us a several years ago. The synthesome from breast cancer cells was shown to contain a unique acidic isoform of PCNA that is present in every malignancy examined to date. Using two-dimensional PAGE, we demonstrated that this unique cancer specific PCNA (csPCNA) has an acidic pI and that it could be selectively bound by the DNA repair protein Xeroderma Pigmentosum G protein (XPG). Using this observation we designed an ELISA assay capable of detecting csPCNA in extracts of malignant breast cells and the sera of late stage breast cancer patients. Our results suggest that this assay may be a useful clinical approach for identifying individuals with breast malignancies and for following the remission status of patients treated for cancer.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]