Journal of Andrology
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Published-Ahead-of-Print June 20, 2007, DOI:10.2164/jandrol.106.002154

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Biphasical effect of androgens on prostate cancer cells and its correlation with androgen receptor coactivator dopa decarboxylase

Shao Chen , Wang yong *, Yue Hong-Hong , Zhang Yun-Tao , Shi Chang-Hong , Liu Fan , Bao Ting-Yi , Yang Zeng-Yue , Yuan Jian-Lin , and Shao Guo-Xing

* To whom correspondence should be addressed. E-mail: dryongwangfmmu{at}yahoo.com.cn.

Aim: Explore the mechanism underlying the dual effect of androgen on prostate cancer cells, and further explore its correlation with dopa decarboxylase, an androgen receptor coactivator and a traditional neuroendocrine differentiateon marker. Methods: After synthetic nonmetabolizable androgen R1881 treatment and confirmation of both the prolific and the shutoff effect by MTT method and flow cytometry, the differential gene expression was analysised by cDNA gene chips. And further explore the correlation between dopa decarboxylase(DDC) expression and the dual effect with gene chip, qRT-PCR, Western-blot and dopa decarboxylase enzyme activity asay. Results: LNCaP cells were inhibited by 10-9M R1881, while stimulated by 10-10M R1881. In the 10-9M R1881 vs. control group chip, we found 320(2.26%) genes expressed differentially, including 170 down-regulated, 150 up-regulated. In the 10-10M vs control group chip, 4608(32.65%) genes expressed differentially, 2562 down-regulated, 2046 up-regulated. The results were confirmed by RT-PCR and Western-blot. In 10-9M R1881(group A) treated group, DDC gene was down-regulated; in 10-10M R1881(group B) and 3x10-8M hydroxyflutamide(group C) treated cells, DDC gene was up-regulated. The enzymic function of DDC in group B and group C was also strengthened. Meanwhile, the NED markers, CgA and synaptophysin, were not affected by AR activators. Conclusion: (1)R1881 could stimulate LNCaP cells' proliferation at 10-10M and below, while inhibited AR through G1/S blockage at 10-9M and above. (2)Androgen receptor coregulators were implicated in the dual effect. The down-regulation of DDC and C4orf1 was involved in the high concentration androgen induced growth inhibition, while the up-regulation of ACTN2, TBLR1 and the down-regulation of FHL2, NCOR1and PIAS3 were involved in the low concentration androgen induced stimulation. (3)DDC could be activated by exogenous AR activators treatment, and its activation is not accompanied by NED markers' up-regulation. Its role as a NED marker deserves further exploration.


Key words: Androgen • Hormone • Prostate • androgen receptor • neuroendocrine defferentiation • prostate cancer






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Copyright © 2007 by The American Society of Andrology.