High Expression of Transient Receptor Potential Channels in Human Breast Cancer Epithelial Cells and Tissues: Correlation with Pathological Parameters
High Expression of Transient Receptor Potential Channels in Human Breast Cancer Epithelial Cells and Tissues: Correlation with Pathological Parameters
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DOI：
10.1159/000335795
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Ouadid-Ahidouch, Halima
中科院分区：
文献类型：
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作者：
Dhennin-Duthille, Isabelle;Gautier, Mathieu;Ouadid-Ahidouch, Halima
背景：瞬时受体电位（Transient Receptor Potential， TRP）通道在许多实体肿瘤中表达。然而，它们在乳腺癌中的表达在很大程度上仍然未知。在这里，我们研究了13个TRP通道在人乳腺导管腺癌（hBDA）中的表达谱，并研究了它们的过表达与病理参数之间的相关性。方法：采用RT-PCR方法检测hBDA组织、人乳腺癌上皮细胞（hBCE）原代培养和MCF-7细胞系中TRP通道的表达。采用免疫组化方法检测59例患者hBDA组织样本中TRP蛋白水平。结果：与邻近非肿瘤组织相比，hBDA中TRPC1、TRPC6、TRPM7、TRPM8和TRPV6通道过表达。最有趣的是，TRPC1、TRPM7和TRPM8的表达与增殖参数（SBR分级、Ki67增殖指数、肿瘤大小）密切相关，TRPV6主要在浸润性乳腺癌细胞中过表达。通过激光捕获显微解剖，我们发现TRPV6在有创区域的表达高于相应的无创区域。此外，TRPV6沉默抑制MDA-MB-231的迁移和侵袭，以及MCF-7的迁移。结论：TRP通道在hBDA、hBCE原代培养和细胞系中表达异常，并与病理参数相关。TRP通道在肿瘤中的高表达表明这些通道在人类乳腺导管腺癌的诊断、预后和/或治疗方法方面具有潜力。巴塞尔S. Karger股份有限公司版权所有
Background: Transient Receptor Potential (TRP) channels are expressed in many solid tumors. However, their expression in breast cancer remains largely unknown. Here, we investigated the profile expression of 13 TRP channels in human breast ductal adenocarcinoma (hBDA) and performed a correlation between their overexpression and pathological parameters. Methods: The TRP channels expression was determined by RT-PCR in hBDA tissue, in human breast cancer epithelial (hBCE) primary culture and in MCF-7 cell line. The TRP protein level was evaluated by immunohistochemistry in hBDA tissue samples of 59 patients. Results: TRPC1, TRPC6, TRPM7, TRPM8, and TRPV6 channels were overexpressed in hBDA compared to the adjacent non-tumoral tissue. Most interestingly, TRPC1, TRPM7 and TRPM8 expression strongly correlated with proliferative parameters (SBR grade, Ki67 proliferation index, and tumor size), and TRPV6 was mainly overexpressed in the invasive breast cancer cells. Using laser capture microdissection, we found that TRPV6 expression was higher in invasive areas, compared to the corresponding non-invasive ones. Moreover, TRPV6 silencing inhibited MDA-MB-231 migration and invasion, and MCF-7 migration. Conclusion: TRP channels are aberrantly expressed in hBDA, hBCE primary cultures, and cell lines, and associated with pathological parameters. The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma. Copyright (C) 2011 S. Karger AG, Basel