Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma

Elaine M. Hurt, Adrian Wiestner, Andreas Rosenwald, A. L. Shaffer, Elias Campo, Tom Grogan, P. Leif Bergsagel, W. Michael Kuehl, Louis M. Staudt

Research output: Contribution to journalArticle

268 Scopus citations

Abstract

The oncogene c-maf is translocated in ~5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin β7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin β7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalCancer cell
Volume5
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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