Departamento de Patologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Programa de Imunologia e Biologia Tumoral, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brasil.
Braz J Med Biol Res. 2023 Feb 10;56:e11879. doi: 10.1590/1414-431X2023e11879. eCollection 2023.
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 CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 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 CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.
T 型电压依赖性钙通道（Cav3）的表达先前已在乳腺癌中观察到，但它们在癌前病变中的表达和亚细胞定位尚未得到评估。因此，本研究旨在评估人乳腺组织样本中 T 型通道同工型的蛋白表达和亚细胞定位。通过免疫组织化学方法评估无改变的乳腺、增生性非肿瘤性病变和人乳腺肿瘤性导管上皮病变中 CaV3.1、CaV3.2 和 CaV3.3 的蛋白表达。在肿瘤转化的晚期，CaV3.1、CaV3.2 和 CaV3.3 的核表达减少，而 CaV3.1 和 CaV3.2 的细胞质表达增加。此外，CaV3.1 同工型的核表达减少与细胞质表达增加相关。CaV3 蛋白表达和亚细胞定位的变化与乳腺上皮细胞的肿瘤转化阶段一致，在早期肿瘤病变中很明显，例如原位导管癌。这些结果表明 CaV3 可能参与了致癌过程，可作为乳腺癌治疗新疗法的潜在药物靶点。
