Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line

  • Authors:
    • Sae Byeol Choi
    • Jong Bae Park
    • Tae-Jin Song
    • Sang Yong Choi
  • View Affiliations

  • Published online on: June 8, 2011     https://doi.org/10.3892/ijmm.2011.719
  • Pages: 449-454
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Abstract

Hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that plays a central role in the hypoxic expression of various genes. Vascular endothelial growth factor (VEGF), a known target gene of HIF-1α, has been shown to be induced by hypoxia through a HIF-1α-independent pathway. HIF-1α dominant-negative lentiviral vectors were introduced to decrease the expression of HIF in Hep3B cells. Cells were incubated under normoxic or hypoxic conditions. We performed a VEGF enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants, and Western blotting using cell lysates. To validate signaling via HIF-1-dependent or HIF-1-independent pathways, we treated cells with an extracellular signal-regulated kinase (ERK) kinase inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, and transfected cells with siSP1. HIF-1α protein expression was induced and the levels of VEGF increased under hypoxic conditions. Cells were transfected with siHIF-1α and incubated under normoxic or hypoxic conditions. We found that a significant amount of VEGF was produced by a HIF-1-independent pathway. PI3K inhibitor treatment and siSP1 transient transfection decreased VEGF expression in siHIF-1α-transfected cells. Therefore, VEGF regulation in Hep3B cells is primarily controlled by the Akt/PI3K and SP1 pathways and is independent of HIF-1 under hypoxic conditions.

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September 2011
Volume 28 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Choi SB, Park JB, Song T and Choi SY: Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line. Int J Mol Med 28: 449-454, 2011.
APA
Choi, S.B., Park, J.B., Song, T., & Choi, S.Y. (2011). Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line. International Journal of Molecular Medicine, 28, 449-454. https://doi.org/10.3892/ijmm.2011.719
MLA
Choi, S. B., Park, J. B., Song, T., Choi, S. Y."Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line". International Journal of Molecular Medicine 28.3 (2011): 449-454.
Chicago
Choi, S. B., Park, J. B., Song, T., Choi, S. Y."Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line". International Journal of Molecular Medicine 28, no. 3 (2011): 449-454. https://doi.org/10.3892/ijmm.2011.719