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

被引:25
作者
Chen, Sufeng [1 ]
Zhang, Jie [1 ]
Li, Xuebing [2 ]
Luo, Xiaoyang [1 ]
Fang, Jing [2 ]
Chen, Haiquan [1 ]
机构
[1] Fudan Univ, Canc Hosp, Inst Canc, Dept Thorac Surg, Shanghai 200032, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China
基金
中国国家自然科学基金;
关键词
Apoptosis; Bax; Bcl-2; Non-small cell lung cancer; Prolyl hydroxylases; HYPOXIA-INDUCIBLE-FACTOR; ENDOTHELIAL GROWTH-FACTOR; HIF; PROTEIN; APOPTOSIS; FAMILY; ACTIVATION; PHYSIOLOGY; ALPHA; PHD3;
D O I
10.1007/s11010-011-0976-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:257 / 263
页数:7
相关论文
共 31 条
[1]   Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor [J].
Appelhoff, RJ ;
Tian, YM ;
Raval, RR ;
Turley, H ;
Harris, AL ;
Pugh, CW ;
Ratcliffe, PJ ;
Gleadle, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (37) :38458-38465
[2]   The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling [J].
Berra, E ;
Ginouvès, A ;
Pouysségur, J .
EMBO REPORTS, 2006, 7 (01) :41-45
[3]   A conserved family of prolyl-4-hydroxylases that modify HIF [J].
Bruick, RK ;
McKnight, SL .
SCIENCE, 2001, 294 (5545) :1337-1340
[4]   Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells [J].
Calvani, Maura ;
Trisciuoglio, Daniela ;
Bergamaschi, Cristina ;
Shoemaker, Robert H. ;
Melillo, Giovanni .
CANCER RESEARCH, 2008, 68 (01) :285-291
[5]   Tumor Vasculature Is Regulated by PHD2-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment [J].
Chan, Denise A. ;
Kawahara, Tiara L. A. ;
Sutphin, Patrick D. ;
Chang, Howard Y. ;
Chi, Jen-Tsan ;
Giaccia, Amato J. .
CANCER CELL, 2009, 15 (06) :527-538
[6]   C-elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation [J].
Epstein, ACR ;
Gleadle, JM ;
McNeill, LA ;
Hewitson, KS ;
O'Rourke, J ;
Mole, DR ;
Mukherji, M ;
Metzen, E ;
Wilson, MI ;
Dhanda, A ;
Tian, YM ;
Masson, N ;
Hamilton, DL ;
Jaakkola, P ;
Barstead, R ;
Hodgkin, J ;
Maxwell, PH ;
Pugh, CW ;
Schofield, CJ ;
Ratcliffe, PJ .
CELL, 2001, 107 (01) :43-54
[7]   EGLN3 prolyl hydroxylase regulates skeletal muscle differentiation and myogenin protein stability [J].
Fu, Jian ;
Menzies, Keon ;
Freeman, Robert S. ;
Taubman, Mark B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (17) :12410-12418
[8]   Expression of prolyl-hydroxylases PHD-1, 2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activated HIF pathway [J].
Giatromanolaki, Alexandra ;
Koukourakis, Michael I. ;
Pezzella, Francesco ;
Turley, Helen ;
Sivridis, Efthimlos ;
Bouros, Demosthenes ;
Bougioukas, George ;
Harris, Adrian L. ;
Gatter, Kevin C. .
CANCER LETTERS, 2008, 262 (01) :87-93
[9]   PHDs overactivation during chronic hypoxia "desensitizes" HIFα and protects cells from necrosis [J].
Ginouves, Amandine ;
Ilc, Karine ;
Macias, Nuria ;
Pouyssegur, Jacques ;
Berra, Edurne .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (12) :4745-4750
[10]   Expression of key hypoxia sensing prolyl-hydroxylases PHD1,-2 and-3 in pancreaticobiliary cancer [J].
Gossage, Lucy ;
Zaitoun, Abed ;
Fareed, Khaleel R. ;
Turley, Helen ;
Aloysius, Mark ;
Lobo, Dileep N. ;
Harris, Adrian L. ;
Madhusudan, Srinivasan .
HISTOPATHOLOGY, 2010, 56 (07) :908-920