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

The expression of T-type voltage-dependent Ca²⁺ 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_V3.1, Ca_V3.2, and Ca_V3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. Ca_V3.1, Ca_V3.2, and Ca_V3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas Ca_V3.1 and Ca_V3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for Ca_V3.1 isoform. The change in Ca_V3 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_V3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Breast cancer; Ductal hyperplasia; Carcinoma in situ; T-type voltage-dependent Ca²⁺ channel; Neoplastic transformation