Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

• Published in: Oncogene Vol. 21; no. 9; pp. 1346 - 1358
• Main Authors: CHAUHAN, Dharminder, AUCLAIR, Daniel, LAN BO CHEN, MUNSHI, Nikhil C, ANDERSON, Kenneth C, ROBINSON, Elisabeth K, HIDESHIMA, Teru, GUILAN LI, PODAR, Klaus, GUPTA, Deepak, RICHARDSON, Paul, SCHLOSSMAN, Robert L, KRETT, Nancy
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 21.02.2002; Nature Publishing Group
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Blotting, Western; Bone marrow; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cancer; Cell death; Cell physiology; Cell survival; Cell Survival - drug effects; Cell Survival - genetics; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cysteine Endopeptidases - metabolism; Cytokines; Dexamethasone; Dexamethasone - pharmacology; DNA microarrays; DNA Repair - drug effects; DNA Repair - genetics; Dosage and administration; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug therapy; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Gene silencing; Genetic aspects; Genetic regulation; Heat-Shock Proteins - genetics; Humans; Kinases; Molecular and cellular biology; Multienzyme Complexes - metabolism; Multiple myeloma; Multiple Myeloma - genetics; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Patient outcomes; Proteasome Endopeptidase Complex; Receptors, Glucocorticoid - genetics; Receptors, Interleukin-6 - genetics; Receptors, Transforming Growth Factor beta - genetics; RNA, Messenger - metabolism; Signal Transduction; Steroids; Transcription; Tumor Cells, Cultured; Tumor necrosis factor-TNF; Ubiquitin - metabolism; Up-Regulation - drug effects; United States; United States > US; Massachusetts; Human; Immunopathology; Dexamethasone; Multiple; Malignant hemopathy; Myeloma; Carcinogenesis; Resistance; Chemotherapy; Treatment; Immunoglobulinopathy; Gene; Lymphoproliferative syndrome; Chemosensitivity
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1205205

Our previous studies have characterized Dexamethasone (Dex)-induced apoptotic signaling pathways in multiple myeloma (MM) cells; however, related transcriptional events are not fully defined. In the present study, gene expression profiles of Dex-treated MM cells were determined using oligonucleotide arrays. Dex triggers early transient induction of many genes involved in cell defense/repair-machinery. This is followed by induction of genes known to mediate cell death and repression of growth/survival-related genes. The molecular and genetic alterations associated with Dex resistance in MM cells are also unknown. We compared the gene expression profiles of Dex-sensitive and Dex-resistant MM cells and identified a number of genes which may confer Dex-resistance. Finally, gene profiling of freshly isolated MM patient cells validates our in vitro MM cell line data, confirming an in vivo relevance of these studies. Collectively, these findings provide insights into the basic mechanisms of Dex activity against MM, as well as mechanisms of Dex-resistance in MM cells. These studies may therefore allow improved therapeutic uses of Dex, based upon targeting genes that regulate MM cell growth and survival.