Intermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status
Intermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status
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DOI：
10.14670/hh-25.1247
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发表时间：
2010-10-01
影响因子：
2
通讯作者：
Ouadid-Ahidouch, Halima
中科院分区：
文献类型：
--
作者：
Haren, Nathalie;Khorsi, Hafida;Ouadid-Ahidouch, Halima
K+通道是多种肿瘤发生发展的关键分子，被认为是肿瘤治疗的潜在靶点使用免疫组织化学方法检测乳腺癌（BC）标本和人乳腺癌上皮原代细胞培养物（hBCE）中hKCa3.1的表达（60个样品）、定量实时RT-PCR（30个样品）和蛋白质印迹测定（30个样品）。我们还研究了这些通道的表达是否与乳腺癌分级、肿瘤和转移状态相关。此外，我们还利用全细胞膜片钳技术对hBCE细胞中hKCa 3.1通道的活性进行了研究，发现hKCa 3.1在BC样品和hBCE细胞中均有表达。临床病理学评价表明hKCa 3.1表达与肿瘤分级显著相关。hKCa 3.1 mRNA和蛋白在III级肿瘤中的表达高于I级和II级肿瘤。然而，hKCa 3.1表达的增加，根据等级，仅观察到在肿瘤转移状态为阴性。此外，在hBCE细胞中表达的hKCa 3.1通道是功能性的。这是证明了膜片钳记录显示典型的hKCa3.1介导的电流在这些细胞。总之，这些数据表明，hKCa3.1可能有助于乳腺肿瘤的进展，并可以作为一个有用的乳腺癌预后标志物。
K+ channels are key molecules in the progression of several cancer types and are considered to be potential targets for cancer therapy.In this study, we investigated the intermediate-conductance Ca2+-activated K+ channels (hKCa3.1) expression in both breast carcinoma (BC) specimens and human breast cancer epithelial primary cell cultures (hBCE) using immuno-histochemistry (60 samples), quantitative Real-Time RT-PCR (30 samples) and Western blot assay (30 samples). We also looked at whether or not the expression of these channels is correlated with breast carcinomas grade tumours and metastasis status. Furthermore, we characterized the hKCa3.1 channel activity in hBCE cells by using the Whole Cell Patch Clamp Technique.We found that hKCa3.1 transcripts and proteins were expressed in both BC samples and hBCE cells. Clinicopathologic evaluation indicated a significant correlation between hKCa3.1-expression and tumour grade. hKCa3.1 mRNA and protein were more highly expressed in grade III tumours than in both grades I and II. However, the hKCa3.1 expression-increase according to grade was only observed in tumours with negative metastasis status. Moreover, the hKCa3.1 channels expressed in hBCE cells are functional. This was attested by patch-clamp recordings showing typical hKCa3.1-mediated currents in these cells. In conclusion, these data suggest that hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer.