T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

Abstract

The expression of T-type voltage-dependent Ca 2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of Ca V 3.1, Ca V 3.2, and Ca V 3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. Ca V 3.1, Ca V 3.2, and Ca V 3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas Ca V 3.1 and Ca V 3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for Ca V 3.1 isoform. The change in Ca V 3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ . These results suggest a possible involvement of Ca V 3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.