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

Oncogene volume 22, pages 2417–2421 (2003)Cite this article

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.

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Acknowledgements

This work was supported by the National Cancer Institute (CA77859 and CA82533 to WSD), and the Peninsula Community Foundation for Myeloma Research. We also thank the H Lee Moffitt Flow Cytometry and Microarray Core Facilities (CA76292).

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Authors and Affiliations

  1. Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, 33612, FL, USA

    Terry H Landowski & William S Dalton

  2. Department of Cell Biology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, 33612, FL, USA

    Nancy E Olashaw & Deepak Agrawal

  3. Department of Medicine, Arizona Cancer Center, University of Arizona, Tucson, 85724, AZ, USA

    Terry H Landowski

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  1. Terry H Landowski
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  2. Nancy E Olashaw
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Correspondence to William S Dalton.

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Landowski, T., Olashaw, N., Agrawal, D. et al. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-κB (RelB/p50) in myeloma cells. Oncogene 22, 2417–2421 (2003). https://doi.org/10.1038/sj.onc.1206315

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