Functional analysis of metallothionein-2A isoform in Breast Cancer

Abstract

Metallothionein (MT) is a cysteine rich, low molecular weight protein and found to be associated with cell proliferation and apoptosis. MT expression has been linked with more aggressive breast cancers. There are ten functional isoforms in human, with MT-2A being the most abundant in breast cancer. The exact roles of the individual MT isoforms in cancer progression have yet to be identified. Silencing and overexpressing MT-2A was shown to have an effect on cell proliferation and metastasis in breast cancer cell lines. Gene expression analysis indicated that MT-2A may regulate breast cancer proliferation and metastasis through the ATM/Chk2/Cdc25a and uPAR pathway, respectively. A significant relationship between MT staining with higher tumor grade, higher lymph node stage, absence of ER and PCNA staining was found in invasive breast carcinomas. Altogether, in vitro and clinical studies show MT-2A has an intimate relationship with cell proliferation and metastasis in breast cancer and proves to be a potential therapeutic target.