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The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer

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Abstract

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.

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Acknowledgments

This work was supported, in part, by the National Natural Science Foundation of China (30800404, 30870524), Shanghai leading academic discipline project (B115), Shanghai municipal natural science fund (06DZ19503), and Basic-clinical medicine grant (to H-Q C), Shanghai Rising-Star Program (09QA1401200), Young investigator grant from the Department of Education in China, the Science and Technology Commission of Shanghai Municipality, IBS Bio-medicine grant from Fudan University (to J. Z.). The authors thank Shannon L. Wyszomierski PhD for the critical review and writing assistance of this article.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Cancer Hospital/Cancer Institute of Fudan University, 270 Dong’an Road, Shanghai, 200032, China

    Sufeng Chen, Jie Zhang, Xiaoyang Luo & Haiquan Chen

  2. Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai, 200031, China

    Xuebing Li & Jing Fang

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  1. Sufeng Chen
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  2. Jie Zhang
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  3. Xuebing Li
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  4. Xiaoyang Luo
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  6. Haiquan Chen
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Correspondence to Haiquan Chen.

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Sufeng Chen, Jie Zhang and Xuebing Li contributed equally to this work.

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Chen, S., Zhang, J., Li, X. et al. The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer. Mol Cell Biochem 358, 257–263 (2011). https://doi.org/10.1007/s11010-011-0976-1

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