Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-κB (RelB/p50) in myeloma cells

Terry H. Landowski, Nancy E. Olashaw, Deepak Agrawal, William S. Dalton

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

The microenvironment has been shown to influence tumor cell phenotype with respect to growth, metastasis, and response to chemotherapy. We have utilized oligonucleotide microarray analysis to identify signal transduction pathways and gene products altered by the interaction of myeloma tumor cells with the extracellular matrix component fibronectin that may contribute to the antiapoptotic phenotype conferred by the microenvironment. Genes with altered expression associated with fibronectin cell adhesion, either induced or repressed, were numerically ranked by fold change. FN adhesion repressed the expression of 469 gene products, while 53 genes with known coding sequences were induced by twofold or more. Of these 53 genes with two fold, or greater increase in expression, 11 have been reported to be regulated by the nuclear factor-kappa B (NF-κB) family of transcription factors. EMSA analysis demonstrated NF-κB binding activity significantly increased in cells adhered to fibronectin compared to cells in suspension. This DNA binding activity consisted primarily of RelB-p50 heterodimers, which was distinct from the NF-κB activation of TNFα. These data demonstrate the selectivity of signal transduction from the microenvironment that may contribute to tumor cell resistance to programmed cell death.

Original languageEnglish (US)
Pages (from-to)2417-2421
Number of pages5
JournalOncogene
Volume22
Issue number16
DOIs
StatePublished - Apr 24 2003

Keywords

  • Adhesion
  • Drug resistance
  • Microarray
  • Myeloma
  • NF-κB

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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