Identification of ID-1 as a potential target gene of MMSET in multiple myeloma
| Autor: | Heidi Rye Hudlebusch, Thomas Rasmussen, Marianne Lodahl, Kim Theilgaard-Mönch, Hans Erik Johnsen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Inhibitor of Differentiation Protein 1
medicine.medical_specialty Transcription Genetic Plasma Cells Cell Chromosomal translocation Biology Transfection Translocation Genetic Malignant transformation Downregulation and upregulation Cell Line Tumor Internal medicine medicine Humans Multiple myeloma Oligonucleotide Array Sequence Analysis Chromosomes Human Pair 14 Hematology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Histone-Lysine N-Methyltransferase Fibroblast growth factor receptor 3 Flow Cytometry medicine.disease Molecular biology Gene Expression Regulation Neoplastic Repressor Proteins medicine.anatomical_structure Gene Targeting Chromosomes Human Pair 4 Carrier Proteins Multiple Myeloma Transcription Factors |
| Zdroj: | University of Copenhagen |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | The frequently detected t(4;14)(p16.3;q32) translocation in multiple myeloma (MM) results in a dysregulation of two potential oncogenes: multiple myeloma SET domain (MMSET) and fibroblast growth factor receptor 3 (FGFR3). As the expression of FGFR3 is undetectable in 30% of the t(4;14)+ MM patients, MMSET has been suggested to play an important role in the malignant transformation associated with the t(4;14) translocation. Screening with a real-time polymerase chain reaction (PCR) found complex expression patterns of the MMSET transcripts in fluorescence-activated cell sorted (FACS)-purified plasma cells (PCs) from 15 t(4;14)+ MM patients. In addition, potential target genes of MMSET type I and II were identified, using microarray analyses of MMSET transfected cell lines. Subsequently, the expression of potential target genes was verified by real-time PCR in FACS-purified PCs from 15 t(4;14)+ and 22 t(4;14)- MM patients. We suggest that the inhibitor of differentiation 1 (ID-1) is a target gene of MMSET, based on its upregulation in MMSET transfected cell lines and a significant association between the t(4;14) translocation and ID-1 expression in MM patients (P = 0.002). As high levels of ID-1 are associated with cancer, our findings indicate that MMSET promotes oncogenic transformation in t(4;14)+ MM patients by transcriptional activation of ID-1 expression. |
| Databáze: | OpenAIRE |
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