gms | German Medical Science

Aims: Prostate cancer is the most common form of cancer in men. Many patients with metastatic prostate carcinoma (PCa) develop resistance to hormone ablation therapy within a few years. The molecular mechanism of this development is still unknown. Our aim was to identify transcriptional changes that are typical features for the transition to hormone resistant prostate cancer (HRPC) using cDNA Microarray technique.

Methods: Fresh frozen tissue samples of 8 patients with HRPC were compared to 8 non-refractory PCa specimens. Palliative received transurethtral resection (TUR) tissue samples with at least 70% tumor cells were macrodissected for RNA extraction. RNA quality was controlled by Agilent Bioanalyzer. Subsequence expression analysis was performed using Affymetrix HG-Focus Arrays.

Results: 282 significantly deregulated genes were identified using SAM algorithm. Among the most affected pathways we identified MAPkinase, Notch and Wnt signalling cascades as well as TGF-β, and Ca2+-signalling. Cell cycle progression is enhanced by down-regulation of tumor suppressor genes like p21 and the induction of Cyclin D1. Furthermore, we detected significant down-regulation of actin cytoskeleton associated genes. In addition, changes in steroid hormone biosynthesis, oxidative phosphorylation and fatty acid metabolism were revealed.

Conclusions: In this study we detected significant deregulated genes in the transition from PCa to HRPC. Further investigation will be needed to validate their potential as clinical biomarkers and therapeutic targets.