Skip to main content
Erschienen in: Pathology & Oncology Research 4/2016

13.04.2016 | Original Article

Strong Correlation Between mRNA Expression Levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in Laryngeal Carcinoma

verfasst von: Todor M. Popov, G. Stancheva, T. E. Goranova, J. Rangachev, D. Konov, S. Todorov, O. Stoyanov, R. P. Kaneva, D. Popova

Erschienen in: Pathology & Oncology Research | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

The hypoxia that arises due to the rapid proliferation of tumor cells is a fundamental driving force for the canonical pathway of neovascularization. In the current study we report a very strong correlation between mRNA expression levels of HIF-2α (but not HIF-1α), VEGFR-1, VEGFR-2 and MMP2 in ex vivo samples from laryngeal carcinoma. Sixty-three samples from patients with histopathologically verified carcinoma of the larynx were examined in this study. Total RNA was isolated from both normal and tumor fresh frozen tissues of each patient and real-time quantitative PCR reactions were performed. The mRNA expression levels of HIF-1α, HIF-2α, VEGFR1, VEGFR2 and MMP2 were acquired. We found strong positive correlations between mRNA expression levels of HIF-2α and VEGFR-1, r s (98) = .671, p < .0005; HIF-2α and VEGFR-2, r s (98) = .742, p < .0005; HIF-2α and MMP2, r s (98) = .566, p < .0005; VEGFR-1 and VEGFR-2, r s (98) = .791, p < .0005; VEGFR-1 and MMP2, r s (98) = .709, p < .0005; VEGFR-2 and MMP2, r s (98) = .793, p < .0005. Our results provide evidence for the regulatory connection between HIF-2α and VEGFR-1, VEGFR-2 and MMP2 in the light of ETS1/ HIF-2α regulatory axis on a non-in-vitro level in carcinoma tissue, uncover some of the differences between the homologues HIF-1α and HIF-2α and round up and support the results from different experimental models in this field.
Literatur
2.
Zurück zum Zitat Fong GH (2008) Mechanisms of adaptive angiogenesis to tissue hypoxia. Angiogenesis 11:121–140CrossRefPubMed Fong GH (2008) Mechanisms of adaptive angiogenesis to tissue hypoxia. Angiogenesis 11:121–140CrossRefPubMed
4.
Zurück zum Zitat Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309CrossRefPubMed Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309CrossRefPubMed
5.
Zurück zum Zitat Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (1990) Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene 5:519–524PubMed Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (1990) Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene 5:519–524PubMed
6.
Zurück zum Zitat Park JE, Chen HH, Winer J, Houck KA, Ferrara N (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654PubMed Park JE, Chen HH, Winer J, Houck KA, Ferrara N (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654PubMed
7.
Zurück zum Zitat Fong GH, Rossant J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66–70CrossRefPubMed Fong GH, Rossant J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66–70CrossRefPubMed
8.
Zurück zum Zitat Robinson CJ, Stringer SE (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114:853–865PubMed Robinson CJ, Stringer SE (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114:853–865PubMed
9.
Zurück zum Zitat Quinn TP, Peters KG, de Vries C, Ferrara N, Williams LT (1993) Fetal liver kinase-1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A 90:7533–7537CrossRefPubMedPubMedCentral Quinn TP, Peters KG, de Vries C, Ferrara N, Williams LT (1993) Fetal liver kinase-1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A 90:7533–7537CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Popov TM, Goranova TE, Stancheva G et al (2015) Relative quantitative expression of HIF-1α, HIF-2α, HIF-3α and VEGF-A in laryngeal carcinoma. Oncol Lett 9:2879–2885PubMedPubMedCentral Popov TM, Goranova TE, Stancheva G et al (2015) Relative quantitative expression of HIF-1α, HIF-2α, HIF-3α and VEGF-A in laryngeal carcinoma. Oncol Lett 9:2879–2885PubMedPubMedCentral
11.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods 25:402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods 25:402–408CrossRefPubMed
12.
Zurück zum Zitat Scrideli CA, Carlotti CG Jr, Okamoto OK et al (2008) Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR. J Neurooncol 88:281–291CrossRefPubMed Scrideli CA, Carlotti CG Jr, Okamoto OK et al (2008) Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR. J Neurooncol 88:281–291CrossRefPubMed
13.
Zurück zum Zitat Borel F, Han R, Visser A et al (2012) Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology 55:821–832CrossRefPubMed Borel F, Han R, Visser A et al (2012) Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology 55:821–832CrossRefPubMed
14.
Zurück zum Zitat Dutta D, Ray S, Vivian JL, Paul S (2008) Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem 283:25404–25413CrossRefPubMedPubMedCentral Dutta D, Ray S, Vivian JL, Paul S (2008) Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem 283:25404–25413CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Hahne JC, Kummer S, Heukamp LC et al (2009) Regulation of protein tyrosine kinases in tumour cells by the transcription factor Ets-1. Int J Oncol 35:989–996PubMed Hahne JC, Kummer S, Heukamp LC et al (2009) Regulation of protein tyrosine kinases in tumour cells by the transcription factor Ets-1. Int J Oncol 35:989–996PubMed
16.
Zurück zum Zitat Elvert G, Kappel A, Heidenreich R et al (2013) Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 278:7520–7530CrossRef Elvert G, Kappel A, Heidenreich R et al (2013) Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 278:7520–7530CrossRef
17.
Zurück zum Zitat Taki M, Verschueren K, Yokoyama K, Nagayama M, Kamata N (2006) Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Int J Oncol 28:487–496PubMed Taki M, Verschueren K, Yokoyama K, Nagayama M, Kamata N (2006) Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Int J Oncol 28:487–496PubMed
18.
Zurück zum Zitat Liu DX, Liu XM, Su Y, Zhang XJ (2011) Renal expression of proto-oncogene Ets-1 on matrix remodeling in experimental diabetic nephropathy. Acta Histochem 113:527–533CrossRefPubMed Liu DX, Liu XM, Su Y, Zhang XJ (2011) Renal expression of proto-oncogene Ets-1 on matrix remodeling in experimental diabetic nephropathy. Acta Histochem 113:527–533CrossRefPubMed
19.
Zurück zum Zitat Eubank TD, Roda JM, Liu H, O’Neil T, Marsh CB (2011) Opposing roles for HIF-1α and HIF-2α in the regulation of angiogenesis by mononuclear phagocytes. Blood 117:323–332CrossRefPubMedPubMedCentral Eubank TD, Roda JM, Liu H, O’Neil T, Marsh CB (2011) Opposing roles for HIF-1α and HIF-2α in the regulation of angiogenesis by mononuclear phagocytes. Blood 117:323–332CrossRefPubMedPubMedCentral
Metadaten
Titel
Strong Correlation Between mRNA Expression Levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in Laryngeal Carcinoma
verfasst von
Todor M. Popov
G. Stancheva
T. E. Goranova
J. Rangachev
D. Konov
S. Todorov
O. Stoyanov
R. P. Kaneva
D. Popova
Publikationsdatum
13.04.2016
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 4/2016
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-016-0059-4

Weitere Artikel der Ausgabe 4/2016

Pathology & Oncology Research 4/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.