Regulation of major histocompatibility complex class I expression by NF-kappaB-related proteins in breast cancer cells

Oncogene. 1998 Jun 25;16(25):3299-307. doi: 10.1038/sj.onc.1201879.

Abstract

Downregulation of MHC Class I antigens has been observed in many cancers and usually results from a decreased gene transcription. A reporter CAT gene dependent on the MHC Class I kappaB site or on a longer promoter is transactivated by NF-kappaB complexes containing p65 or RelB. p100 as well as IkappaB-alpha are potent inhibitors of this transcription and p100 sequesters RelB and p65 complexes in the cytoplasm of breast cancer cells. However, although p100 is highly expressed in a number of breast cancer cell lines, MHC Class I antigen expression was observed on all the cell lines we analysed and could be further induced by stimulation with the cytokines IFN-gamma or TNF-alpha. Stable transfection of a unresponsive mutated IkappaB-alpha Ser 32-36 expression vector showed that TNF-alpha induced MHC Cl I expression in an NF-kappaB-dependent way while IFN-gamma did it independently of any NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Binding Sites / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I / drug effects
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • I-kappa B Proteins*
  • Interferon-gamma / pharmacology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics
  • NF-kappa B / pharmacology
  • NF-kappa B / physiology*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins*
  • Recombinant Proteins / genetics
  • Transcription Factor RelB
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Histocompatibility Antigens Class I
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Recombinant Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Transcription Factor RelB
  • Interferon-gamma