The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots.
The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots.
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DOI：
10.1186/1476-4598-5-17
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发表时间：
2006-05-15
期刊：
影响因子：
37.3
通讯作者：
Franklin, Renty B
中科院分区：
文献类型：
--
作者：
Costello, Leslie C;Franklin, Renty B
恶性前列腺细胞的发生和发展的遗传和分子机制尚不清楚。此外，尽管它在几乎所有的恶性细胞中都有影响，但细胞代谢改变作为前列腺癌的一个基本因素的作用在很大程度上被忽视了。此外，正常前列腺和恶性前列腺细胞的中间代谢是所有哺乳动物细胞中研究最少、了解最少的细胞之一。一些重要的因素，特别是锌的作用，已经被发现并与恶性肿瘤的发生和发展有关。在这篇综述中，我们对正常前列腺和前列腺癌中间代谢的关系提供了最新的综合评估。介绍了导致正常和恶性前列腺代谢概念形成的实验和临床证据。描述了锌作为肿瘤抑制因子和ZIP1锌转运体作为肿瘤抑制基因这一概念的证据。正常前列腺腺上皮产生和分泌极高水平的柠檬酸的特殊功能涉及并需要独特的中间代谢活动，这些活动通常与其他正常哺乳动物细胞不相关。这些细胞对锌的积累是这种独特代谢关系中的一个重要因素。在恶性肿瘤中，正常的积累锌的柠檬酸产生的上皮细胞被代谢转化为柠檬酸氧化细胞，后者失去积累锌的能力。ZIP1锌转运蛋白表达的基因改变与这种代谢转化有关。这些遗传/代谢关系对柠檬酸相关代谢、生物能量学、细胞增殖和恶性肿瘤细胞的侵袭能力有重要影响，从而导致肿瘤抑制特性。正常前列腺腺上皮的遗传/代谢关系是由积累和分泌柠檬酸的独特功能驱动的。前列腺恶性细胞的遗传/代谢转化是由恶性过程的代谢/生物能量、生长/增殖和侵袭/迁移要求驱动的。锌对这些关系至关重要。对这些遗传/代谢关系的了解为前列腺癌的预防和治疗方案的开发提供了新的方向和机会。对前列腺癌过程的遗传/代谢要求的重要洞察现在正在演变。目前最重要的是，认识和认识遗传/代谢在前列腺癌发生发展中的意义和意义是当务之急；这方面的研究也是非常必要的。希望这项审查将有助于实现这些目标。
The genetic and molecular mechanisms responsible for and associated specifically with the development and progression of malignant prostate cells are largely unidentified. In addition, despite its implication in virtually all malignant cells, the role of altered cellular metabolism as an essential factor in prostate malignancy has been largely ignored. Moreover, the intermediary metabolism of normal prostate as well as malignant prostate cells is among the least studied and most poorly understood of all mammalian cells. Some important factors, especially the role of zinc, have been identified and implicated in the development and progression of prostrate malignancy. In this review, we provide a current and updated integrated assessment of the relationships of intermediary metabolism in normal prostate and in prostate cancer. The experimental and clinical evidence that leads to the formulation of concepts of normal and malignant prostate metabolism is presented. The evidence for a concept of zinc as a tumor suppressor agent and Zip1 zinc transporter as a tumor-suppressor gene is described. The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. The accumulation of zinc by these cells is an essential factor in this unique metabolic relationship. In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. A genetic alteration in the expression of ZIP1 zinc transporter is associated with this metabolic transformation. These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunities for development of regimens for the prevention and treatment of prostate cancer. Important insight into the genetic/metabolic requirements of the prostate malignant process is now evolving. Most importantly at this time, an appreciation and recognition of the genetic/metabolic significance and implications in the development of prostate malignancy is imperative; and much needed research in this area is essential. Hopefully, this review will help to achieve these goals.