AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells

Oncol Rep. 2010 Aug;24(2):547-54.


BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis / radiation effects*
  • Base Sequence
  • Blood Proteins / antagonists & inhibitors
  • Blood Proteins / genetics
  • Blood Proteins / physiology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins
  • RNA, Small Interfering / pharmacology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • bcl-Associated Death Protein / genetics*
  • bcl-Associated Death Protein / metabolism


  • BAD protein, human
  • Blood Proteins
  • MLLT11 protein, human
  • NF-kappa B
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • bcl-Associated Death Protein