Zhang Lei, Barritt Gregory J
Office of Chemical Safety (MDP 88), Therapeutic Goods Administration, Department of Health and Ageing, PO Box 100, Woden ACT 2606, Australia.
Endocr Relat Cancer. 2006 Mar;13(1):27-38. doi: 10.1677/erc.1.01093.
During the past 5 years it has emerged that the transient receptor potential (TRP) family of Ca(2+)-and Na(+)-permeable channels plays a diverse and important role in cell biology and in pathology. One member of this family, TRPM8, is highly expressed in prostate cancer cells but the physiological and pathological functions of TRPM8 in these cells are not known. Here we address these questions, and the issue of whether or not TRPM8 is an effective diagnostic and prognostic marker in prostate cancer. TRPM8 is known to be activated by cool stimuli (17-25 degrees C) and cooling compounds such as menthol. The activation mechanism(s) involves voltage sensing of membrane potential, phosphatidylinositol 4,5-bisphosphate and Ca(2+). In addition to prostate cancer cells, TRPM8 is expressed in sensory neurons where it acts as a sensor of cold. In prostate epithelial cells, expression of TRPM8 is regulated by androgen and is elevated in androgen-sensitive cancerous cells compared with normal cells. While there is some evidence that in prostate cancer cells Ca(2+) and Na(+) inflow through TRPM8 is necessary for survival and function, including secretion at the apical membrane, the function of TRPM8 in these cells is not really known. It may well differ from the role of TRPM8 as a cool sensor in sensory nerve cells. Androgen unresponsive prostate cancer is difficult to treat effectively and there are limited diagnostic and prognostic markers available. TRPM8 is a potential tissue marker in differential diagnosis and a potential prognostic marker for androgen-unresponsive and metastatic prostate cancer. As a consequence of its ability to convey Ca(2+) and Na(+) and its expression in only a limited number of cell types, TRPM8 is considered to be a promising target for pharmaceutical, immunological and genetic interventions for the treatment of prostate cancer.
在过去5年中，已发现瞬时受体电位（TRP）家族的钙和钠通透性通道在细胞生物学和病理学中发挥着多样且重要的作用。该家族的一个成员TRPM8在前列腺癌细胞中高度表达，但TRPM8在这些细胞中的生理和病理功能尚不清楚。在此，我们探讨这些问题，以及TRPM8是否为前列腺癌有效的诊断和预后标志物。已知TRPM8可被冷刺激（17 - 25摄氏度）和薄荷醇等冷却化合物激活。其激活机制涉及膜电位的电压传感、磷脂酰肌醇4,5 - 二磷酸和钙离子。除前列腺癌细胞外，TRPM8还表达于感觉神经元中，在那里它作为冷感受器发挥作用。在前列腺上皮细胞中，TRPM8的表达受雄激素调节，与正常细胞相比，在雄激素敏感的癌细胞中其表达升高。虽然有一些证据表明，在前列腺癌细胞中，通过TRPM8的钙和钠内流对细胞存活和功能（包括顶端膜分泌）是必要的，但TRPM8在这些细胞中的功能实际上并不清楚。它很可能与TRPM8在感觉神经细胞中作为冷感受器的作用不同。雄激素无反应性前列腺癌难以有效治疗，可用的诊断和预后标志物有限。TRPM8是鉴别诊断中的潜在组织标志物，也是雄激素无反应性和转移性前列腺癌的潜在预后标志物。由于其能够转运钙和钠，且仅在有限数量的细胞类型中表达，TRPM8被认为是治疗前列腺癌的药物、免疫和基因干预的一个有前景的靶点。
