Dhennin-Duthille Isabelle, Gautier Mathieu, Faouzi Malika, Guilbert Arnaud, Brevet Marie, Vaudry David, Ahidouch Ahmed, Sevestre Henri, Ouadid-Ahidouch Halima
Laboratoire de Physiologie Cellulaire, JE 2530, UFR Sciences, Université de Picardie Jules Verne, Amiens, France.
Cell Physiol Biochem. 2011;28(5):813-22. doi: 10.1159/000335795. Epub 2011 Dec 15.
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.
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.
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.
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.
瞬时受体电位(TRP)通道在许多实体瘤中均有表达。然而,它们在乳腺癌中的表达情况仍 largely 未知。在此,我们研究了 13 种 TRP 通道在人乳腺导管腺癌(hBDA)中的表达谱,并对其过表达与病理参数进行了相关性分析。
通过 RT-PCR 测定 hBDA 组织、人乳腺癌上皮(hBCE)原代培养物及 MCF-7 细胞系中 TRP 通道的表达。通过免疫组织化学评估 59 例患者 hBDA 组织样本中的 TRP 蛋白水平。
与相邻的非肿瘤组织相比,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 增殖指数和肿瘤大小)密切相关,且 TRPV6 主要在浸润性乳腺癌细胞中过表达。使用激光捕获显微切割技术,我们发现与相应的非浸润区域相比,TRPV6 在浸润区域的表达更高。此外,TRPV6 沉默抑制了 MDA-MB-231 细胞的迁移和侵袭以及 MCF-7 细胞的迁移。
TRP 通道在 hBDA、hBCE 原代培养物及细胞系中异常表达,并与病理参数相关。肿瘤中 TRP 通道的高表达提示这些通道在人乳腺导管腺癌的诊断、预后和/或治疗方法方面具有潜力。