| First Author | Lu LY | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 46 | Pages | 31785-90 |
| PubMed ID | 18801727 | Mgi Jnum | J:143099 |
| Mgi Id | MGI:3822929 | Doi | 10.1074/jbc.M805880200 |
| Citation | Lu LY, et al. (2008) Aurora A is essential for early embryonic development and tumor suppression. J Biol Chem 283(46):31785-90 |
| abstractText | Aurora A is a serine/threonine kinase that functions in various stages of mitosis. Accumulating evidence has demonstrated that gene amplification and overexpression of Aurora A are linked to tumorigenesis, suggesting that Aurora A is an oncogene. In addition, Aurora A overexpression has been used as a negative prognostic marker, because it is associated with resistance to anti-mitotic agents commonly used for cancer therapy. To understand the physiological functions of Aurora A, we generated Aurora A knock-out mice. Aurora A null mice die early during embryonic development before the 16-cell stage. These Aurora A null embryos have defects in mitosis, particularly in spindle assembly, supporting critical functions of Aurora A during mitotic transitions. Interestingly, Aurora A heterozygosity results in a significantly increased tumor incidence in mice, suggesting that Aurora A may also act as a haploinsufficient tumor suppressor. Consistently, Aurora A heterozygous mouse embryonic fibroblasts have higher rates of aneuploidy. We further discovered that VX-680, an Aurora kinase inhibitor currently in phase II clinical trials for cancer treatment, could induce aneuploidy in wild type mouse embryonic fibroblasts. We conclude that a balanced Aurora A level is critical for maintaining genomic stability and one needs to be fully aware of the potential side effects of anti-cancer therapy based on the use of Aurora A-specific inhibitors. |
