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Hypoxia Inducible Factor-1 beta and Cancer Development

Mon, 10/15/2012 - 10:24

Hypoxia inducible factor-1 (HIF-1) is a major transcription factor that is composed of two subunits: HIF-1 alpha and HIF-1 beta, the latter being a constitutively-expressed aryl hydrocarbon receptor nuclear transporter (ARNT). Under normoxic conditions, HIF-1 beta is constitutively expressed and HIF-1 alpha is targeted to proteosomal degradation via ubiquitination. On the other hand during hypoxic conditions when oxygen concentration is low, HIF-1 alpha is stabilized and translocates to nucleus, where it dimerizes with HIF-1 beta to form functional HIF-1. This altered redox state occurs in the cells experiencing hypoxia leading to gene transcription of several angiogenic factors (1).

IHC analysis of HIF-1 beta

In a recent study it was demonstrated that widespread expression of HIF-1 beta occurs in developing and mature kidneys as determined by immunohistochemistry (IHC) using anti-HIF-1 beta antibodies, compared to HIF-2 beta. The differential distribution pattern suggests divergent roles during the kidney development (2). To investigate the pleiotropic responses of HIF-1 in lung cancers paraffin embedded tissues from human lungs were probed for HIF-1 subunits by IHC using anti HIF-1 antibodies suggesting that HIF-1 plays an important role during the angiogenesis in tumor growth and progression (3). With a growing knowledge of the molecular mechanisms in the field, novel strategies to prevent tumor angiogenesis can be developed leading to new anticancer therapies.

  1. PMID: 18922400
  2. PMID: 1546626
  3. PMID: 12542982

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