Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma cells

Physiological Genomics - Tập 22 Số 3 - Trang 308-318 - 2005
Ajith Vengellur1,2, J. M. Phillips1, John B. Hogenesch3, John J. LaPres4,1,5
1§Department of Biochemistry and Molecular Biology
2Graduate Program in Genetics, Michigan State University, East Lansing, Michigan
3The Genomics Institute of the Novartis Research Foundation, San Diego, California.
4†Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan
5National Food Safety and Toxicology Center

Tóm tắt

Cellular, local, and organismal responses to low O2availability occur during processes such as anaerobic metabolism and wound healing and pathological conditions such as stroke and cancer. These responses include increases in glycolytic activity, vascularization, breathing, and red blood cell production. These responses are mediated in part by the hypoxia-inducible factors (HIFs), which receive information on O2levels from a group of iron- and O2-dependent hydroxylases. Hypoxia mimics, such as cobalt chloride, nickel chloride, and deferoxamine, act to simulate hypoxia by altering the iron status of these hydroxylases. To determine whether these mimics are appropriate substitutes for the lower O2tension evoked naturally, we compared transcriptional responses of a Hep3B cell line using high-density oligonucleotide arrays. A battery of core genes was identified that was shared by all four treatments (hypoxia, cobalt, nickel, and deferoxamine) including glycolytic enzymes, cell cycle regulators, and apoptotic genes. Importantly, cobalt, nickel, and deferoxamine influenced transcription of distinct sets of genes that were not affected by cellular hypoxia. These global responses to hypoxia indicate a balancing act between adaptation and programmed cell death and suggest caution in the use of hypoxia mimics as substitutes for the low O2tension that occurs in vivo.

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Tài liệu tham khảo

10.1093/emboj/cdg392

10.1128/MCB.12.12.5373

10.1126/science.1066373

10.1152/physrev.1996.76.3.839

10.1016/S0006-291X(03)00453-4

10.1016/S0092-8674(01)00507-4

10.1038/sj.bjp.0704933

10.2174/1389200043335577

10.1186/gb-2004-5-10-r80

10.1016/S1357-4310(97)01198-2

Griffiths JR, McSheehy PM, Robinson SP, Troy H, Chung YL, Leek RD, Williams KJ, Stratford IJ, Harris AL, and Stubbs M.Metabolic changes detected by in vivo magnetic resonance studies of HEPA-1 wild-type tumors and tumors deficient in hypoxia-inducible factor-1β (HIF-1β): evidence of an anabolic role for the HIF-1 pathway.Cancer Res62: 688–695, 2002.

10.1146/annurev.pharmtox.40.1.519

10.1038/sj.cdd.4400810

10.1096/fj.02-0582fje

Ihaka Rand Gentlemen R.R: a language for data analysis and graphics.J Comp Graph Stats5: 299–314, 1996.

10.1101/gad.12.2.149

10.1126/science.1059796

Jiang Y, Zhang W, Kondo K, Klco JM, St Martin TB, Dufault MR, Madden SL, Kaelin WG Jr, and Nacht M.Gene expression profiling in a renal cell carcinoma cell line: dissecting VHL and hypoxia-dependent pathways.Mol Cancer Res1: 453–462, 2003.

10.1074/jbc.270.22.13333

Luster AD, Weinshank RL, Feinman R, and Ravetch JV.Molecular and biochemical characterization of a novel γ-interferon-inducible protein.J Biol Chem263: 12036–12043, 1988.

10.1242/jcs.00318

10.1002/(SICI)1098-2264(200002)27:2<169::AID-GCC8>3.0.CO;2-M

10.1016/S1367-5931(02)00302-2

Salnikow K, Davidson T, Zhang Q, Chen LC, Su W, and Costa M.The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis.Cancer Res63: 3524–3530, 2003.

10.1086/320595

10.1073/pnas.88.13.5680

Semenza GL, Roth PH, Fang HM, and Wang GL.Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.J Biol Chem269: 23757–23763, 1994.

10.1128/MCB.22.7.2283-2293.2002

10.1152/physiolgenomics.00104.2002

10.1002/path.1486

10.1093/toxsci/kfh278

10.3727/000000003108749062

Wu Z, Irizarry RA, Gentlemen R, Murillo FM, and Spencer F.A Model-Based Background Adjustment for Oligonucleotide Expression Arrays(2004). http://www.bepress.com/jhubiostat/paper1.

10.1038/sj.onc.1204012

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Physiological Genomics

Tập 22 Số 3

308-318

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