Royds J A, Dower S K, Qwarnstrom E E, Lewis C E
Institute of Cancer Studies, University of Sheffield Medical School, UK.
Mol Pathol. 1998 Apr;51(2):55-61. doi: 10.1136/mp.51.2.55.
Hypoxia is present in several areas of malignant tumours and is thought to result from an inadequate rate of tumour angiogenesis, vascular collapse, or both. The presence and extent of these hypoxic tumour microenvironments have recently been shown to influence tumour progression by regulating both tumour cell survival and the expression of key angiogenic molecules. Recent studies have suggested that mutations in the tumour suppressor gene, p53, may play an important role in regulating the adaptive response of tumour cells to hypoxia by enhancing their survival and release of proangiogenic factors such as vascular endothelial growth factor. It has even been suggested that hypoxia may select for the survival of the more malignant clones harbouring such genetic defects as mutations in p53. Recently, the transcription factor, NFkB, has also been implicated as a novel mediator of the effects of hypoxia and reoxygenation in tumour cells. This article reviews some of the molecular mechanisms subserving the responses of tumour cells to hypoxic stress, particularly the role and relation of NFkB and p53 in regulating this phenomenon.
缺氧存在于恶性肿瘤的多个区域，被认为是肿瘤血管生成速率不足、血管塌陷或两者共同作用的结果。最近研究表明，这些缺氧肿瘤微环境的存在和程度通过调节肿瘤细胞存活以及关键血管生成分子的表达来影响肿瘤进展。最近的研究提示，肿瘤抑制基因p53的突变可能通过增强肿瘤细胞存活以及促血管生成因子（如血管内皮生长因子）的释放，在调节肿瘤细胞对缺氧的适应性反应中发挥重要作用。甚至有人提出，缺氧可能会选择具有诸如p53突变等遗传缺陷的更具恶性的克隆存活下来。最近，转录因子NFkB也被认为是肿瘤细胞中缺氧和复氧效应的一种新型介质。本文综述了一些维持肿瘤细胞对缺氧应激反应的分子机制，特别是NFkB和p53在调节这一现象中的作用及关系。
