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Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. : Androgen receptor and TRPM8 in human prostate apical epithelial cells

机译:人前列腺分泌上皮细胞中特定TRPM8表达的证据:功能性雄激素受体的需求。 :人前列腺顶上皮细胞中的雄激素受体和TRPM8

摘要

TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.
机译:阳离子通道的瞬时受体电位(TRP)超家族的成员TRPM8(美拉他汀相关的瞬时受体电位成员8)已被证明是钙通道蛋白。 TRPM8 mRNA也已显示在前列腺癌中过表达,并被认为在前列腺生理中起重要作用。这项研究旨在确定TRPM8 mRNA表达的雄激素调节机制,并确定人前列腺中TRPM8表达细胞的表型。我们的发现表明,trpm8基因表达需要功能性雄激素受体。此外,本文强烈支持trpm8基因是主要的雄激素响应基因这一事实。单细胞逆转录酶PCR和免疫组织化学实验还表明trpm8基因主要在人前列腺的根尖分泌上皮细胞中表达,并且在原代培养的人前列腺上皮细胞的根尖分化表型丧失期间发生trpm8下调。 。雄激素调节的trpm8表达机制对于了解前列腺癌向雄激素非依赖性的进展至关重要。这些发现可能有助于设计从TRPM8 mRNA水平预测前列腺癌状态的策略。此外,由于TRPM8通道位于人前列腺细胞中,因此了解其在正常前列腺中的生理功能以及其在前列腺癌发展中的潜在作用将很有趣。

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