期刊
ONCOGENE
卷 29, 期 10, 页码 1531-1542出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.442
关键词
ezrin; c-Myc; metastasis; cell invasion; androgen
资金
- Novo Nordisk Foundation Center for Protein Research
- Karolinska Institutet, Cancerfonden [45576-B01-01XAB]
- Swedish Research Council [VR- 529-2002-6766]
- Robert Lundberg Memorial Foundation [2007Lund0045]
The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals involve the modulation of Akt and GSK-3 beta activity resulting in increased c-Myc protein synthesis and inhibition of its degradation. In summary, we have shown a key role for ezrin as a mediator of c-Myc-induced tumorigenesis in prostate cancer cells. Oncogene (2010) 29, 1531-1542; doi:10.1038/onc.2009.442; published online 14 December 2009
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