Transcription alterations of genes of the Ubiquitin-Proteasome Pathway in Prostate Carcinoma

Abstract

The profuse cellular processes controlled by the ubiquitin-proteasome degradation network make it a target for diverse human pathologies including cancerogenesis. (Devoy et al. 2005; Mani and Gelmann 2005) Aberrations in the UPP were investigated by comparing transcript expression patterns of ten members of the system pathway in tumour and adjacent normal tissue of prostate carcinoma patients: eight of these transcripts are ubiquitin E3 ligases (UBE3A, NEDD4, HECW1, SMURF2, CBL, MDM2, SIAH1) and the other two, PSMC4 and PSMB5, belong to the two major components of the proteasome, the 19S regulator and 20S protease core respectively. Three of the transcripts investigated, PSMC4, PSMB5 and NEDD4L, demonstrated significant up-regulation of expression in cancer cells compared to adjacent normal prostate tissue. Their dysregulation display the potential role of these transcripts in prostate tumourigenesis and progression. This study elaborated on the potential mechanism of NEDD4L action via regulation of TGF-ß signalling in prostate cancer pathogenesis and further discussed the role of NEDD4L in androgen action in the prostate. In addition, selective intervention in PSMB5 and NEDD4L action could provide novel therapeutic approaches for treatment of human prostate carcinoma.