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Author: Vaish M.
作者：Vaish M.
Resource: Mol Cancer. 2007 Apr 2;6:26.
2005 IF:
源自：《肿瘤分子学》。2007年4月2日；6:26
Abstract: For the exceptional self-renewal capacity, regulated cell proliferation and differential potential to a wide variety of cell types, the stem cells must maintain the intact genome. The cells under continuous exogenous and endogenous genotoxic stress accumulate DNA errors, drive proliferative expansion and transform into cancer stem cells with a heterogeneous population of tumor cells. These cells are a common phenomenon for the hematological malignancies and solid tumors. In response to DNA damage, the complex cellular mechanisms including cell cycle arrest, transcription induction and DNA repair are activated. The cells when exposed to cytotoxic agents, the apoptosis lead to cell death. However, the absence of repair machinery makes the cells resistant to tumor sensitizing agents and result in malignant transformation. Mismatch repair gene defects are recently identified in hematopoietic malignancies, leukemia and lymphoma cell lines. This review emphasizes the importance of MMR systems in maintaining the stem cell functioning and its therapeutic implications in the eradication of cancer stem cells and differentiated tumor cells as well. The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures.
摘要:为了有特殊的自我更新能力，规律的细胞增殖和分化为多种细胞类型的特定潜能，干细胞必须保持完整的基因组。细胞在持续的外源和内源具有遗传毒性的刺激下积聚了DNA错误，从而驱使细胞增殖扩张并转化成肿瘤异质化的肿瘤干细胞。这些细胞发生改变的行为，对于恶性血液病及实体肿瘤来说是一种很普遍的现象。 为了应对DNA损伤，细胞有一套复杂的机制，包括细胞周期停滞，诱导转录和DNA修复被激活。当细胞暴露在毒素剂下时，凋亡导致细胞死亡。然而，由于缺乏细胞抵抗肿瘤致敏修复装置，而导致癌变。错配修复基因缺陷是最近在造血系统恶性肿瘤，白血病和淋巴瘤细胞株中被发现的。这次评论重点强调了，MMR系统在维持干细胞的功能及其在肿瘤干细胞根除和肿瘤细胞分化上的治疗意义等。错配修复对干细胞及其恶性相似物生物功能的理解，这将有助于制定一套有效的新型疗法，以此去除残留下的，在潜在肿瘤治疗中最终会成为肿瘤的非至瘤细胞。
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发表于 2007-5-22 20:23:17