Department of Thoracic Surgery, Cancer Hospital/Cancer Institute of Fudan University, Shanghai 200032, China.
Mol Cell Biochem. 2011 Dec;358(1-2):257-63. doi: 10.1007/s11010-011-0976-1. Epub 2011 Jul 12.
The prolyl hydroxylase domain enzymes (PHDs) play the most notable role in cellular oxygen sensing and oxygen homeostasis, the transcription of PHD genes are involved in the protection against hypoxia and oxidative stress. Intratumoral hypoxia exists in malignant solid tumors primarily due to rapid cancer cell proliferation with high metabolic demands and defective structural and functional vasculature. Previous studies have demonstrated that all the three PHDs have the ability to hydroxylate hypoxia inducible factor (HIF) polypeptides, which are the key molecules in maintaining the oxygen homeostasis. However, PHDs play multiple physiological and pathological roles. There is scant data regarding expression of PHDs genes in non-small cell lung cancer (NSCLC) tissues. In Addition, the relationship between PHDs and apoptosis has never been explored in NSCLC. In this article, we examined the expression of PHD genes and their relationship with the tumor behavior and apoptosis-associated factors in NSCLC. Our results indicated that the expression of PHDs was much higher in lung cancer tissue than that of adjacent normal tissue, and the high expression of PHD3 was associated with early tumor stage and well differentiation in NSCLC. Moreover, increased PHD3 expression was significantly correlated with the low expression of Bcl-2, suggesting its potential role in inducing apoptosis.
脯氨酰羟化酶结构域酶（PHDs）在细胞氧感应和氧平衡中起着最重要的作用，PHD 基因的转录参与了对缺氧和氧化应激的保护。肿瘤内缺氧主要存在于恶性实体肿瘤中，这主要是由于癌细胞快速增殖，代谢需求高，结构和功能血管缺陷。先前的研究表明，所有三种 PHD 都有能力使缺氧诱导因子（HIF）多肽羟化，HIF 多肽是维持氧平衡的关键分子。然而，PHD 发挥着多种生理和病理作用。关于非小细胞肺癌（NSCLC）组织中 PHDs 基因的表达数据很少。此外，PHDs 与 NSCLC 中的细胞凋亡之间的关系从未被探索过。在本文中，我们研究了 PHD 基因的表达及其与 NSCLC 中肿瘤行为和凋亡相关因素的关系。我们的结果表明，PHDs 在肺癌组织中的表达明显高于邻近正常组织，PHD3 的高表达与 NSCLC 中的早期肿瘤分期和良好分化有关。此外，PHD3 表达的增加与 Bcl-2 的低表达显著相关，提示其在诱导细胞凋亡中的潜在作用。
