Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma
Authors:
Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, Bergsagel PL, Kuehl WM and Staudt LM
In:
Source:
Cancer Cell
Publication Date:
(
2004
)
Issue:
5
:
191-199
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
NCI-H929 [H929]
Species: human
Tissue Origin: blood
Experiment
In the human multiple myeloma cell line H929, reduction of c-maf expression was achieved by nucleofection with a c-maf siRNA construct. As an effect, monitored by RT-PCR, the mRNA of three target genes was also knocked down. In addition, decreased surface expression of one of these target genes was detected.
Abstract
The oncogene c-maf is translocated in approximately 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 beta7, 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 beta7 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.
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