V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: Involvement of HIF-1 in tumor progression

Bing Hua Jiang, Faton Agani, Antonino Passaniti, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

Adaptation to hypoxia represents an important aspect of tumor progression. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates essential homeostatic responses to cellular and systemic hypoxia by activating transcription of multiple genes including those encoding glycolytic enzymes and vascular endothelial growth factor (VEGF). In this report, we demonstrate that whereas C-SRC expression is not required for expression of HIF-1 or transcriptional activation of genes encoding VEGF and enolase 1 (ENO1), cells expressing the v-Src oncogene have increased expression of HIF-1, VEGF, and ENO1 under both hypoxic and nonhypoxic conditions. Expression of V-SRC was associated with increased transcription of reporter genes containing cis-acting hypoxia-response elements from the VEGF and ENO1 genes, and this transcriptional activation required an intact HIF-1 binding site. When three rat hepatoma subclones that differed with respect to the level of HIF-1 expression were injected into nude mice, tumor growth correlated with HIF-1 expression, suggesting that HIF-1 maybe generally involved in tumor progression. These studies link an oncogene to the induction of HIF-1 expression, thus providing a mechanism for hypoxic adaptation by tumor cells.

Original languageEnglish (US)
Pages (from-to)5328-5335
Number of pages8
JournalCancer Research
Volume57
Issue number23
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: Involvement of HIF-1 in tumor progression'. Together they form a unique fingerprint.

  • Cite this