Other
12 Authors
- Costa M,
- Dai W,
- Jiang N,
- Bai J,
- Winkles JA,
- Brown SA,
- Huang Y,
- Shen R,
- Lu L,
- Yang Y,
- Alberts GF,
- Komissarova E
| First Author | Yang Y | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 11 | Pages | 4077-85 |
| PubMed ID | 18519666 | Mgi Jnum | J:136425 |
| Mgi Id | MGI:3796300 | Doi | 10.1158/0008-5472.CAN-07-6182 |
| Citation | Yang Y, et al. (2008) Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions. Cancer Res 68(11):4077-85 |
| abstractText | Polo-like kinase 3 (Plk3) is an important mediator of the cellular responses to genotoxic stresses. In this study, we examined the physiologic function of Plk3 by generating Plk3-deficient mice. Plk3(-/-) mice displayed an increase in weight and developed tumors in various organs at advanced age. Many tumors in Plk3(-/-) mice were large in size, exhibiting enhanced angiogenesis. Plk3(-/-) mouse embryonic fibroblasts were hypersensitive to the induction of hypoxia-inducible factor-1 alpha (HIF-1 alpha) under hypoxic conditions or by nickel and cobalt ion treatments. Ectopic expression of the Plk3-kinase domain (Plk3-KD), but not its Polo-box domain or a Plk3-KD mutant, suppressed the nuclear accumulation of HIF-1 alpha induced by nickel or cobalt ions. Moreover, hypoxia-induced HIF-1 alpha expression was tightly associated with a significant down-regulation of Plk3 expression in HeLa cells. Given the importance of HIF-1 alpha in mediating the activation of the 'survival machinery' in cancer cells, these studies strongly suggest that enhanced tumorigenesis in Plk3-null mice is at least partially mediated by a deregulated HIF-1 pathway. |
