Kategorie: Onkologická diagnostika
Téma: 05. Prognostické a prediktivní faktory I
Číslo abstraktu: 019
Autoři: H. Neuwirt
To investigate possible effects of androgens on SOCS-3 protein expression, PC3-AR and the androgen-dependent LAPC-4 cells were treated with different concentrations of R1881. Our Western blot analyses show an increase in expression of the SOCS-3 protein after androgen treatment in both cell lines, which can be blocked by the anti-androgen bicalutamide. To further characterize effects of R1881 on SOCS-3 gene, qRT-PCR and promoter-reporter assay were performed. Surprisingly, we find no influence of androgen on SOCS-3 mRNA levels or promoter activity, thus suggesting a post-transcrip-tional effect of androgens. Hence, we blocked translation or transcription by using cycloheximide and actinomycin D, respectively. Concordant with our previous findings we show a significant increase of SOCS-3 protein level after androgen treatment in cells in which transcription was blocked, but not in those with impaired translation. In order to understand implications of SOCS-3 regulation by androgen, we used the SOCS-3 negative LNCaP-ATCC and stably transfected them with a tetracycline-responsible SOCS-3 Tet-On plasmid. We report that androgenic proliferative effects on cell proliferation and PSA secretion are significantly diminished following upregulation of SOCS-3 protein.
In conclusion, androgens upregulate SOCS-3 protein via post-transcriptional effects and SOCS-3 itsself inhibits androgen-stimulated proliferation, possibly by influencing cell cycle regulation.
This abstract was sponsored by the Austrian Research Fund (FWF), grant number: 18193
Datum přednesení příspěvku: 29. 11. 2007