Hypoxia and Prx1 in Malignant Progression of Prostate Cancer
Annual rept. 1 Sep 2006-31 Aug 2007
ROSWELL PARK CANCER INST BUFFALO NY
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Hypoxia has been proposed to function as a microenvironmental pressure to select for a subset of cancer cells with an increased ability to survive and proliferate. The activation of Nrf2 and the up-regulation of prx1 expression by changes of oxygenation are likely to contribute to the malignant progression of cancer and to modify the treatment response of cancer cells. The information provided in the current study suggests that the Nrf2-Prx1 axis may serve as a fruitful target for cancer prognosis and therapy. Identifying the key regulatory components and understanding the molecular basis of prx1 gene regulation by Nrf2 are critical to the development of intervention strategies. Future research will be aimed at finding out whether Nrf2-Prx1 activation can be suppressed by genetic andor pharmacological approaches, and whether suppressing the Nrf2-Prx1 axis will inhibit the malignant progression or reverse treatment resistance in pre-clinical models. We provide the first evidence that suggests hypoxia increases AR function in human prostate cancer cells, and Prx1 enhances the hypoxia-mediated AR activation. Delineating the molecular mechanisms by which hypoxia affects AR function will provide insight into the treatment resistance and malignant progression of prostate cancer cells. Novel therapeutic approaches should be developed to prevent hypoxia andor its consequences to enhance the efficacy of androgen deprivation therapy, a treatment that has not been Improved significantly since its introduction over 50 years ago.
- Medicine and Medical Research