The upregulation of protein disulfide isomerase (PDI) and its potential usage in drug-targeted therapy for breast cancer

Abstract

Breast cancer is the leading cause of cancer death among women worldwide. As of the end of 2020, there were 2.3 million women diagnosed with breast cancer and 685 000 deaths globally. Chemotherapy is a common treatment for breast cancer although it was known to be associated with many side effects. It is believed that such treatment can be improved by drug targeted therapy. Recently we have carried out a preliminary study on proteomics analysis of 25 pair of surgically removed breast cancerous tissues and normal tissues from patients. Differentially proteins expression between the types of tissues was done by 2D-gel electrophoresis separation followed by protein profiles mapping. The identity of the targeted protein spots was analysed by LC/MS/MS and protein database search. The data was then confirmed by Western blots. Subsequently, immunocytostaining experiments were carried out to determine the cellular location of the targeted proteins. A few proteins were found significantly (p <0.05) upregulated > 2 folds in breast cancerous tissues compared to breast normal tissues. Two of the up-regulated proteins, namely HSP60 and PDI were upregulated in stage 2, stage 3, T2, T3, N2, and N3 breast cancers. The immunocytostaining revealed the extracellular location of these proteins, while the strong immunoreactivity of PDI with its anti-PDI antibody marked it as a usefulness target for breast cancer therapy.