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Publication : Evidence of a role for antizyme and antizyme inhibitor as regulators of human cancer.

First Author  Olsen RR Year  2011
Journal  Mol Cancer Res Volume  9
Issue  10 Pages  1285-93
PubMed ID  21849468 Mgi Jnum  J:205402
Mgi Id  MGI:5544721 Doi  10.1158/1541-7786.MCR-11-0178
Citation  Olsen RR, et al. (2011) Evidence of a role for antizyme and antizyme inhibitor as regulators of human cancer. Mol Cancer Res 9(10):1285-93
abstractText  Antizyme and its endogenous antizyme inhibitor have recently emerged as prominent regulators of cell growth, transformation, centrosome duplication, and tumorigenesis. Antizyme was originally isolated as a negative modulator of the enzyme ornithine decarboxylase (ODC), an essential component of the polyamine biosynthetic pathway. Antizyme binds ODC and facilitates proteasomal ODC degradation. Antizyme also facilitates degradation of a set of cell cycle regulatory proteins, including cyclin D1, Smad1, and Aurora A kinase, as well as Mps1, a protein that regulates centrosome duplication. Antizyme has been reported to function as a tumor suppressor and to negatively regulate tumor cell proliferation and transformation. Antizyme inhibitor binds to antizyme and suppresses its known functions, leading to increased polyamine synthesis, increased cell proliferation, and increased transformation and tumorigenesis. Gene array studies show antizyme inhibitor to be amplified in cancers of the ovary, breast, and prostate. In this review, we summarize the current literature on the role of antizyme and antizyme inhibitor in cancer, discuss how the ratio of antizyme to antizyme inhibitor can influence tumor growth, and suggest strategies to target this axis for tumor prevention and treatment.
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