Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line
- Authors
- Choi, Sae Byeol; Park, Jung Bae; Song, Tae-Jin; Choi, Sang Yong
- Issue Date
- 9월-2011
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- hepatocellular carcinoma; Hep3B cell line; angiogenesis; vascular endothelial growth factor; hypoxia-inducible factor-1; SP1
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.28, no.3, pp.449 - 454
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
- Volume
- 28
- Number
- 3
- Start Page
- 449
- End Page
- 454
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/111699
- DOI
- 10.3892/ijmm.2011.719
- ISSN
- 1107-3756
- 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-1 alpha, has been shown to be induced by hypoxia through a HIF-1 alpha-independent pathway. HIF-1 alpha 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 HIFI-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-1 alpha protein expression was induced and the levels of VEGF increased under hypoxic conditions. Cells were transfected with siHIF-1 alpha 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-1 alpha-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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