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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2667-2673. Prepublished online as a Blood First Edition Paper on July 2, 2007; DOI 10.1182/blood-2005-11-026344. This Article Full Text (PDF) All Versions of this Article: blood-2005-11-026344v1 110/7/2667    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawamata, N. Articles by Koeffler, H P. Search for Related Content PubMed PubMed Citation Articles by Kawamata, N. Articles by Koeffler, H P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2005 Accepted June 2, 2007 SAHA (vorinostat) suppresses translation of cyclin D1 in mantle cell lymphoma cells Norihiko Kawamata*, John Chen, and H Phillip Koeffler Division of Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA, United States * Corresponding author; email: kawamatan{at}cshs.org. Mantle cell lymphoma (MCL) has a chromosomal translocation resulting in the expression of the cyclin D1 gene driven by the powerful enhancer of the immunoglobulin heavy chain gene leading to uncontrolled, overexpressed cyclin D1 protein. We showed that suberoylanilide hydroxamic acid (SAHA, vorinostat), one of the histone deacetylase (HDAC) inhibitors derived from hydroxamic acid, caused a dramatic decrease (90 %) in protein levels of cyclin D1 after 8 hours exposure to SAHA (5 µM) in MCL lines (SP49, SP53, Jeko1). Messenger RNA levels and protein stability of cyclin D1 were minimally affected by SAHA over 8 hours. In contrast, metabolic labeling assays showed that SAHA decreased incorporation of [35S]-methionine into cyclin D1 protein. The drug also decreased levels of phosphorylated Akt, mTOR, and eIF4E-BP and lowered the cap site binding activity of eIF4E in the MCL cells. In vitro phosphatidyl inositol (PI) kinase assay demonstrated that SAHA directly inhibited kinase activity of PI 3' kinase. Taken together, SAHA caused a rapid decrease of cyclin D1 in MCL by blocking the translation of cyclin D1 by inhibiting the PI3K/Akt/mTOR/eIF4E-BP pathway, probably by PI3K inhibition. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Gupta, S. M. Ansell, A. J. Novak, S. Kumar, S. H. Kaufmann, and T. E. Witzig Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2 Blood, October 1, 2009; 114(14): 2926 - 2935. [Abstract] [Full Text] [PDF] C. J. Chou, D. Herman, and J. M. Gottesfeld Pimelic Diphenylamide 106 Is a Slow, Tight-binding Inhibitor of Class I Histone Deacetylases J. Biol. Chem., December 19, 2008; 283(51): 35402 - 35409. [Abstract] [Full Text] [PDF] R. W. Chen, L. T. Bemis, C. M. Amato, H. Myint, H. Tran, D. K. Birks, S. G. Eckhardt, and W. A. Robinson Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma Blood, August 1, 2008; 112(3): 822 - 829. [Abstract] [Full Text] [PDF] O. A. O'Connor Mantle Cell Lymphoma: Identifying Novel Molecular Targets in Growth and Survival Pathways Hematology, January 1, 2007; 2007(1): 270 - 276. [Abstract] [Full Text] [PDF]

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