L-type voltage-dependent Ca2+ channels expression involved in pre-neoplastic transformation of breast cancer

Abstract

Abstract Background Intracellular Ca2+ levels can modulate several cellular functions, including proliferation and other processes found altered in neoplastic cells. Helping to maintain Ca2+ homeostasis, L-type voltage-dependent Ca2+ channels had its expression identified in neoplasias, including breast cancer. Invasive breast carcinoma of no special type, the most common classification of breast cancer, has ductal hyperplasia and ductal carcinoma in situ as its possible non-obligate precursors. This channel’s role in breast cancer development from these precursors has not been investigated. Evaluate protein expression and subcellular localization of CaV1.1, CaV1.2, and CaV1.3 in mammary epithelium without alteration and neoplastic and non-neoplastic ductal proliferative lesions through immunohistochemistry was the aim of this investigation. Methods In the present study, CaV1.1, CaV1.2, and CaV1.3 protein expression was evaluated by immunohistochemistry in breast without alteration and in proliferative non-neoplastic and neoplastic ductal epithelial lesions of the human breast. Results It was observed that CaV1.3 presented a reduction in nuclear expression at neoplastic lesions, in addition to an increase in cytoplasmic CaV1.1 expression. The analyses of membrane immunostaining showed that CaV1.2 and CaV1.3 had an increase of expression as the lesions progressed in the stages leading to invasive carcinomas. Conclusions Changes in protein expression and subcellular localization of these channels during the progression stages indicate that they may be involved in neoplastic transformation.

Keywords

• Breast cancer
• Ductal hyperplasia
• Carcinoma in situ
• L-type voltage-dependent Ca2+ channel
• LTCC
• Neoplastic transformation