Achieving hypoxia-inducible gene expression in tumors

L Marignol, M Lawler, Mary Coffey, D Hollywood, Mark Lawler

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Hypoxia is an inevitable feature of solid tumors and a common cause of treatment failure. Hypoxia acts as a trigger to genetic instability, apoptosis and possibly metastases. The adaptive response to cellular hypoxia involves the modulation of the synthesis of multiple proteins controlling processes such as glucose homeostasis, angiogenesis, vascular permeability and inflammation. The hypoxia responsive element (HRE) sequences isolated from oxygen-responsive genes have been shown to selectively induce gene expression in response to hypoxia when placed upstream of a promoter. The levels of induced gene expression were dependent on the number of HRE copies and the oxygen tension. Hypoxia-mediated cancer gene therapy strategies may represent a promising mean to significantly improve the efficacy of standard radiation therapy and chemotherapy approaches.

Original languageEnglish
Pages (from-to)359-64
Number of pages6
JournalCANCER BIOLOGY & THERAPY
Volume4
Issue number4
Publication statusPublished - Apr 2005

Keywords

  • Animals
  • Cell Hypoxia
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Humans
  • Hypoxia-Inducible Factor 1
  • Models, Biological
  • Neoplasms
  • Neoplasms, Experimental
  • Response Elements

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