Análise da imunoexpressão dos canais de Ca2+ dependentes de voltagem do tipo L e T em proliferações epiteliais ductais neoplásicas e não neoplásicas na mama humana

Abstract

Breast cancer is considered the tumour with the highest incidence among women, besides being responsible for the highest number of deaths caused by cancer in this part of the population. Among the various histological classifications, invasive ductal carcinoma is the most common and it was suggested that its neoplastic transformation occurs in steps, defining hyperplasic ductal lesions and ductal carcinomas in situ, as alterations predecessor to their development. These epithelial lesions have in common changes in cell proliferation, a process highly controlled by cyclins, cyclin-dependent kinases and also by the intracellular concentration of calcium ions. Ca2+ is a second messenger whose signalling can regulate, in addition to proliferation, several cellular functions, such as apoptosis, migration and gene transcription, which are all involved in changes found in neoplastic cells. Ca2+ signalling is dependent on the increase of its intracellular concentration, that dependent on transporting proteins, such as the L-type voltage-dependent Ca2+ channels (CaV1.1, CaV1.2, CaV1.3 and CaV1.4) and the T-type (CaV3.1, CaV3.2 and CaV3.3). These channels are generally associated with excitable cells, but their presence has already been seen in non-excitable tissues, including tumour cells. Also, its mRNA expression has already been seen altered in neoplasms, indicating the participation of L and T-type channels in neoplastic development. However, its expression behaviour and its subcellular location have not been described in the mammary epithelium without alteration and in proliferative, non-neoplastic and neoplastic ductal epithelial lesions of the human breast, which is the main objective of this work. For this, the protein expression of CaV1.1, CaV1.2, CaV1.3, CaV3.1, CaV3.2 and CaV3.3 was evaluated, using the immunohistochemistry technique in the mammary epithelium without alteration, ductal hyperplasias and ductal carcinomas in situ and invasive. It was possible to observe a reduction in the nuclear expression of L-type and T-type channels in neoplastic lesions, except for CaV1.2, which does not have its expression altered. Besides, there is an increase in the cytoplasmic expression of the CaV3.1 and CaV3.2, among the processes of neoplastic transformation of the mammary epithelium. Surprisingly, only the CaV1.2, CaV1.3 and CaV3.3 isoforms showed membrane expression, indicating that in the other isoforms these channels are not present in the cell membrane, suggesting their participation through other subcellular compartments. The results show the presence and possible participation of L and T-type voltage-dependent Ca2+ channels in the neoplastic transformation to invasive ductal carcinomas and point to a possible way of control and early treatment of breast cancer.