| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
We have investigated the cloning and characterization of the novel splicing variant, p120β for p120α which is a nuclear general receptor co-activator. We have found that p120β was expressed predominantly in androgen responsive prostate cancers but not in recurrent cancers. Our previous findings suggest that p120β plays a role in the androgen sensitivity of prostate cancer, and that the expression ratio of p120 β/α may reflect different androgen sensitivity.
In this study, we analyzes the effects of p120β on androgen resistant of prostate cancers. First we made PC3 cells expressing the intact androgen receptor. We confirmed that the tranfected androgen receptor into PC3 cells functionally worked. However, the expression ration of p120α and p120β were not changed between the wild type PC3 cells and the AR-induced PC3 cells suggesting that the expression of intact AR is not associated with the change of expression of p120. Next to determine whether the decreasing of p120α expression change the androgen sensitivity, we tried to do RNA interference assay using the specific probes of p120α. Only 25 % of inhibition of the expression levels of p120α was observed in RT-PCR method. However, our RNA interference probes inhibits 30 % of the lucifrase activity of MMTV promoter vector in the presence of DHT of the intact AR expressed PC3 cells, indicating the endogenous p120 may regulate the AR-induced gene activation. Finally, we demonstrated the functional difference between p120 and p120β in PC3 cells. Incubation with other ligands for nuclear receptors significantly inhibited the DHT induced transactivation by p120α, but not by p120β. This phenomenon may explain the mechanism by which the p120α may pull to other nuclear receptors in the presence of certain ligands, implying that p120β but not α may be a specific co-activator for AR in the PC3 cells.
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