This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mistry, S. J. Articles by Atweh, G. F. Search for Related Content PubMed PubMed Citation Articles by Mistry, S. J. Articles by Atweh, G. F.

Division of Hematology-Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York

Requests for reprints: Sucharita J. Mistry or George F. Atweh, Division of Hematology-Oncology, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. Phone: 212-241-5293; E-mail: sucharit.mistry{at}mssm.edu or george.atweh{at}mssm.edu

Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin is expressed at high levels in a variety of human cancers and provides an attractive molecule to target in cancer therapies that disrupt the mitotic apparatus. We developed replication-deficient bicistronic adenoviral vectors that coexpress green fluorescent protein and ribozymes that target stathmin mRNA. The therapeutic potential of these recombinant adenoviruses was tested in an experimental androgen-independent LNCaP prostate cancer model. Adenovirus-mediated transfer of anti-stathmin ribozymes resulted in efficient transduction and marked inhibition of stathmin expression in these cells. Cells that were transduced with the anti-stathmin adenoviruses showed a dramatic dose-dependent growth inhibition. This was associated with accumulation of LNCaP cells in the G₂-M phases of the cell cycle. A similar dose-dependent inhibition of clonogenic potential was also observed in cells infected with anti-stathmin adenoviruses. Morphologic and biochemical analysis of infected cells showed a marked increase in apoptosis characterized by detachment of the cells, increased chromatin condensation, activation of caspase-3, and fragmentation of internucleosomal DNA. If these findings are confirmed in vivo, it may provide an effective approach for the treatment of prostate cancer. [Mol Cancer Ther 2005;4(12):1821–9]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/29/05; revised 9/ 8/05; accepted 10/13/05.

This article has been cited by other articles:

				S. J. Mistry, A. Bank, and G. F. Atweh Synergistic Antiangiogenic Effects of Stathmin Inhibition and Taxol Exposure Mol. Cancer Res., August 1, 2007; 5(8): 773 - 782. [Abstract] [Full Text] [PDF]

				K. M.R. Bhat and V. Setaluri Microtubule-Associated Proteins as Targets in Cancer Chemotherapy Clin. Cancer Res., May 15, 2007; 13(10): 2849 - 2854. [Abstract] [Full Text] [PDF]

				S. J. Mistry and G. F. Atweh Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer Mol. Cancer Ther., December 1, 2006; 5(12): 3248 - 3257. [Abstract] [Full Text] [PDF]

				P. Holmfeldt, K. Brannstrom, S. Stenmark, and M. Gullberg Aneugenic Activity of Op18/Stathmin Is Potentiated by the Somatic Q18->E Mutation in Leukemic Cells Mol. Biol. Cell, July 1, 2006; 17(7): 2921 - 2930. [Abstract] [Full Text] [PDF]