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 language | English (US) |
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Pages (from-to) | 191-199 |
Number of pages | 9 |
Journal | Cancer cell |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2004 |
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research