Abstract
Aim:
To explore the mechanism of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in the lung adenocarcinoma A549 cell line and its relationship with hypoxia-inducible factor 1α (HIF-1α).
Methods:
DEC1 and HIF-1α protein levels were detected in lung adenocarcinoma tissues by immunohistochemistry. A549 cells were cultured at hypoxia. MTT assay was used to determine the effect of cell viability. The apoptotic analysis was determined by flow cytometry. RT-PCR and immunocytochemistry were carried out to observe the DEC1 and HIF-1α mRNA and protein expression. HIF-1α mRNA and protein levels were detected in the stably transfected pcDNA-DEC1+/- A549 cells by RT-PCR and Western blotting. DEC1 mRNA and protein levels were detected in the stably transfected pcDNA-DEC1+/- A549 cells with or without HIF-1α antisense oligonucleotide treatment by RT-PCR and Western blotting.
Results:
DEC1 was specifically located in 40 (48.8%) lung adenocarcinoma tissues. The results of the MTT test showed the growth of the stably transfected pcDNA-DEC+ A549 cells was higher than those of A549 cells and the stably transfected pcDNA-DEC- A549 cells. Hypoxia also induced the apoptosis of A549 cells and the stably transfected pcDNA-DEC+/- A549 cells. Hypoxia increased the mRNA and protein levels of DEC1 and HIF-1α. Both HIF-1α mRNA and protein levels decreased in the stably transfected pcDNA-DEC+ cells, but HIF-1α antisense oligonucleotide had no effect on DEC1 in the stably transfected pcDNA-DEC+/- A549 cells.
Conclusion:
DEC1 is a marker of tumor hypoxia. DEC1 downregulates the HIF-1α at both mRNA and protein levels at hypoxia in lung adenocarcinoma A549 cells.
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Brown, JM, The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain memorial award lecture. Cancer Res 1999; 59: 5863–70.
Shannon, AM, Bouchier-Hayes, DJ, Condron, CM, Toomey, D, Tumor hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 2003; 29: 297–307.
Harris, AL, Hypoxia-a key regulatory factor in tumor growth. Nat Rev Cancer 2002; 2: 38–47.
Maxwell, PH, Pugh, CW, Ratcliffe, PJ, Activation of the HIF pathway in cancer. Curr Opin Genet 2001; 11: 293–9.
Goonewardene, TI, Sowter, HM, Harris, AL, Hypoxia-induced pathways in breast cancer. Microsc Res Tech 2002; 59: 41–8.
Pugh, CW, Ratcliffe, PJ, The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis. Semin Cancer Biol 2003; 13: 83–9.
Chakrabarti, J, Turley, H, Campo, L, Han, C, Harris, AL, Gatter, KC, et al. The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumor grade in human breast cancers. Br J Cancer 2004; 91: 954–8.
Dagnon, K, Pacary, E, Commo, F, Antoine, M, Bernaudin, M, Bernaudin, JF, et al. Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas. Clin Cancer Res 2005; 11: 993–9.
Hanahan, D, Weinberg, RA, The hallmarks of cancer. Cell 2000; 100: 57–70.
Shen, M, Kawamoto, T, Yan, W, Nakamasu, K, Tamagami, M, Koyano, Y, et al. Molecular characterization of the novel basic helix-loop-helix protein DEC1 expressed in differentiated human embryo chondrocytes. Biochem Biophys Res Commun 1997; 236: 294–8.
Rossner, MJ, Dorr, J, Gass, P, Schwab, MH, Nave, KA, SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled to neuronal stimulation. Mol Cell Neurosci 1997; 9: 460–75.
Boudjelal, M, Taneja, R, Matsubara, S, Bouillet, P, Dolle, P, Chambon, P, Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells. Genes Dev 1997; 11: 2052–65.
Teramoto, M, Nakamasu, K, Noshiro, M, Matsuda, Y, Gotoh, O, Shen, M, et al. Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1. Stra13. SHARP-2/BHLHB2. J Biochem 2001; 129: 391–6.
Li, Y, Zhang, H, Xie, M, Hu, M, Ge, S, Yang, D, et al. Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation. Biochem J 2002, 367: 413–22.
Ivanova, AV, Ivanov, SV, Danilkovitch-Miagkova, A, Lerman, MI, Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway. J Biol Chem 2001; 276: 15306–15.
Giatromanolaki, A, Koukourakis, MI, Sivridis, E, Turley, H, Wykoff, CC, Gatter, KC, et al. DEC1 (STRA13) protein expression relates to hypoxia-inducible factor 1-alpha and carbonic anhydrase-9 overexpression in non-small cell lung cancer. J Pathol 2003; 200: 222–8.
Turley, H, Wykoff, CC, Troup, SS, The hypoxia-regulated transcription factor DEC1 (Stra13, SHARP-2) and its expression in human tissues and tumors. J Pathol 2004, 203: 808–13.
Caniggia, I, Mostachfi, H, Winter, J, Gassmann, M, Lye, SJ, Kuliszewski, M, et al. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J Clin Invest 2000; 105: 577–87.
Behar-Cohen, FF, David, T, Buechler, Y, Nova, MP, Houston, LL, Pouliquen, YM, et al. Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro. Invest Ophthalmol Vis Sci 1995; 36: 2425–33.
Han, SW, Lei, ZM, Rao, CV, Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua. Endocrinology 1996; 137: 1791–7.
Wykoff, CC, Pugh, CW, Maxwell, PH, Harris, AL, Ratcliffe, PJ, Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumor suppressor by mRNA differential expression profiling. Oncogene 2000; 19: 6297–305.
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Zhang, L., Li, Qq. Embryo-chondrocyte expressed gene 1, downregulating hypoxia-inducible factor 1α, is another marker of lung tumor hypoxia. Acta Pharmacol Sin 28, 549–558 (2007). https://doi.org/10.1111/j.1745-7254.2007.00516.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00516.x
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