Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays

Dharminder Chauhan, Guilan Li, Daniel Auclair, Teru Hideshima, Paul Richardson, Klaus Podar, Nicholas Mitsiades, Constantine Mitsiades, Cheng Li, Ryung S. Kim, Nikhil Munshi, Lan Bo Chen, Wing Wong, Kenneth C. Anderson

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Our previous study demonstrated that 2-methoxyestradiol (2ME2), an estrogen derivative, induces apoptosis in multiple myeloma (MM) cells; however, the related transcriptional events are unclear. In the present study, we used oligonucleotide microarrays to identify genes altered during 2ME2-induced apoptosis in MM cells. 2ME2 triggers an early transient induction of genes known to trigger cell death and repression of growth/survival-related genes. Many genes regulating cell defense/repair machinery also were transiently induced. Since 2ME2 also induces apoptosis in MM cells resistant to conventional therapies such as dexamethasone (Dex), we compared the gene profiles of 2ME2-treated and Dex-resistant MM cells. Our results suggest that 2ME2 overcomes Dex resistance by modulating genes that confer chemoresistance in MM cells. Microarray results were confirmed by Northern and Western blot analyses. A comparative analysis of selected genes from freshly isolated MM patient cells and 2ME2-treated MM.1S MM cells further provides an in vivo relevance of our in vitro studies. Collectively, these findings suggest genetic events mediating anti-MM activity of 2ME2, as well as mechanisms whereby 2ME2 overcomes Dex resistance in MM cells. These studies may therefore allow improved therapeutic use of 2ME2, based upon targeting genes that regulate MM cell growth and survival.

Original languageEnglish (US)
Pages (from-to)3606-3614
Number of pages9
JournalBlood
Volume101
Issue number9
DOIs
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Oligonucleotide Array Sequence Analysis
Multiple Myeloma
Oligonucleotides
Genes
Dexamethasone
Microarrays
Apoptosis
2-methoxyestradiol
Cell growth
Cell death
Gene Targeting
Machinery
Therapeutic Uses
Growth
Estrogens
Repair
Northern Blotting
Derivatives
Cell Survival
Cell Death

ASJC Scopus subject areas

  • Hematology

Cite this

Chauhan, D., Li, G., Auclair, D., Hideshima, T., Richardson, P., Podar, K., ... Anderson, K. C. (2003). Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays. Blood, 101(9), 3606-3614. https://doi.org/10.1182/blood-2002-10-3146

Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays. / Chauhan, Dharminder; Li, Guilan; Auclair, Daniel; Hideshima, Teru; Richardson, Paul; Podar, Klaus; Mitsiades, Nicholas; Mitsiades, Constantine; Li, Cheng; Kim, Ryung S.; Munshi, Nikhil; Chen, Lan Bo; Wong, Wing; Anderson, Kenneth C.

In: Blood, Vol. 101, No. 9, 01.05.2003, p. 3606-3614.

Research output: Contribution to journalArticle

Chauhan, D, Li, G, Auclair, D, Hideshima, T, Richardson, P, Podar, K, Mitsiades, N, Mitsiades, C, Li, C, Kim, RS, Munshi, N, Chen, LB, Wong, W & Anderson, KC 2003, 'Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays', Blood, vol. 101, no. 9, pp. 3606-3614. https://doi.org/10.1182/blood-2002-10-3146
Chauhan, Dharminder ; Li, Guilan ; Auclair, Daniel ; Hideshima, Teru ; Richardson, Paul ; Podar, Klaus ; Mitsiades, Nicholas ; Mitsiades, Constantine ; Li, Cheng ; Kim, Ryung S. ; Munshi, Nikhil ; Chen, Lan Bo ; Wong, Wing ; Anderson, Kenneth C. / Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays. In: Blood. 2003 ; Vol. 101, No. 9. pp. 3606-3614.
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