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

Oncogene volume 21, pages 1346–1358 (2002)Cite this article

Abstract

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.

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Acknowledgements

This investigation was supported by NIH CA 78373 awarded by the National Cancer Institute, Multiple Myeloma Research Foundation Senior Research Scientist Awards (D Chauhan, T Hideshima), and a Doris Duke Distinguished Clinical Research Scientist Award (KC Anderson).

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Author notes

  1. Dharminder Chauhan and Daniel Auclair: D Chauhan and D Auclair contributed equally to this work.

Authors and Affiliations

  1. Department of Adult Oncology, The Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Dharminder Chauhan, Teru Hideshima, Guilan Li, Klaus Podar, Deepak Gupta, Paul Richardson, Robert L Schlossman, Nikhil C Munshi & Kenneth C Anderson

  2. Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Daniel Auclair, Elisabeth K Robinson & Lan Bo Chen

  3. Northwestern University Medical School, Robert H Lurie Cancer Center, Chicago, Illinois, USA

    Nancy Krett

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  1. Dharminder Chauhan
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  2. Daniel Auclair
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  3. Elisabeth K Robinson
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  4. Teru Hideshima
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Correspondence to Kenneth C Anderson.

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Chauhan, D., Auclair, D., Robinson, E. et al. Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays. Oncogene 21, 1346–1358 (2002). https://doi.org/10.1038/sj.onc.1205205

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