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

Sae Byeol Choi, Jong Bae Park, Tae Jin Song, Sang Yong Choi

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalInternational journal of molecular medicine
Issue number3
Publication statusPublished - 2011 Sept
Externally publishedYes


  • Angiogenesis
  • Hep3B cell line
  • Hepatocellular carcinoma
  • Hypoxia-inducible factor-1
  • SP1
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Genetics


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