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中等电导钙激活钾通道在乳腺腺癌中表达和功能:与肿瘤分级和转移状态的相关性。

Intermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status.

机构信息

LPCM JE 2530, UPJV, Amiens, France.

出版信息

Histol Histopathol. 2010 Oct;25(10):1247-55. doi: 10.14670/HH-25.1247.

Abstract

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.

摘要

钾通道是几种癌症类型进展的关键分子,被认为是癌症治疗的潜在靶点。在这项研究中,我们使用免疫组织化学(60 个样本)、实时定量 RT-PCR(30 个样本)和 Western blot 检测(30 个样本)研究了乳腺癌(BC)标本和人乳腺癌上皮原代细胞培养物(hBCE)中中电导钙激活钾通道(hKCa3.1)的表达情况。我们还观察了这些通道的表达是否与乳腺癌肿瘤的分级和转移状态有关。此外,我们通过全细胞膜片钳技术对 hBCE 细胞中的 hKCa3.1 通道活性进行了表征。我们发现 hKCa3.1 转录本和蛋白在 BC 样本和 hBCE 细胞中均有表达。临床病理评估表明 hKCa3.1 表达与肿瘤分级之间存在显著相关性。与 I 级和 II 级肿瘤相比,III 级肿瘤中 hKCa3.1 mRNA 和蛋白的表达水平更高。然而,仅在无转移状态的肿瘤中观察到根据分级的 hKCa3.1 表达增加。此外,在 hBCE 细胞中表达的 hKCa3.1 通道是功能性的。这一点通过膜片钳记录得到证实,这些细胞中显示出典型的 hKCa3.1 介导的电流。总之,这些数据表明 hKCa3.1 可能有助于乳腺癌的进展,可以作为乳腺癌的一个有用的预后标志物。

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