Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell malignancy.
MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the monokine induced by interferon-gamma(MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/leukemia by regulating the expression of various genes including MIG. Leukemia (2005) 19, 1471-1478. doi:10.1038/sj.leu.2403833; published online 16 June 2005.
Uranishi
M
M
Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Iida
S
S
Sanda
T
T
Ishida
T
T
Tajima
E
E
Ito
M
M
Komatsu
H
H
Inagaki
H
H
Ueda
R
R
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050835:Interferon Regulatory Factors; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics*; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C485969:Cxcl9 protein, mouse