These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here.
Of note, rs7000448 is in strong linkage disequilibrium with rs10761581 in NCOA4, a SNP that has been implicated to be independently associated, with respect to the widely reported SNP rs10993994 in the nearby gene MSMB, with prostate cancer in men of European descent.
The changes in expression pattern of AR and AR cofactors and in particular the remarkable increase in AR, ARA160 and ARA70 support the role of AR cofactors in modulating prostate cancer cell growth from androgen dependence to androgen independence.
Because ARA70-N2 containing the AR-interacting FXXLF motif without coactivation function can suppress HF-enhanced AR transactivation in the hormone-refractory LNCaP cells, using the ARA70-N2 inhibitory peptide at the hormone refractory stage to battle the HF withdrawal syndrome may become an alternative strategy to treat prostate cancer.
We identified ARA70, a coactivator of the androgen receptor and PPARgamma, as a ligand-enhanced coactivator of PPARalpha in the prostate cancer cell line DU145.
Characterization of the functional relationship between the AR and these coregulators indicated that ARA70 and ARA55 could enhance the androgenic effects of 17beta-estradiol (E2) and hydroxyflutamide (HF), an antiandrogen commonly used in the treatment of prostate cancer.
Reduced levels of RFG/ELE1alpha/ARA70 message were observed in all four prostate cancer cell lines when compared with normal PrECs in primary cultures.
Furthermore, our results suggest that among the LBD coregulators, ARA70 has a relatively high specificity for AR in the human prostate cancer cell line DU145.