Interaction of REPS2 with NF-kappaB in Prostate Cancer Cells
Like normal prostate cells, prostate cancer cells are dependent on androgens for growth and survival, and prostate cancer can be treated by androgen ablation therapy. However, after a period of time some of the prostate cancer cells no longer respond to androgen ablation and survive the therapy. This transition of androgen-dependent prostate cancer (ADPC) to androgen-independent prostate cancer (AIPC) is critical, since no effective therapy is available for the androgen-independent stage of the disease. The molecular mechanisms that underlie the transition are largely unknown. REPS2, the protein that is studied in this PhD thesis project, might be involved in a molecular mechanism that contributes to AIPC development, since REPS2 mRNA is downregulated in AIPC compared to ADPC. With specific antibodies it was shown that the REPS2 protein level in AIPC is decreased compared to ADPC. Transient overexpression of REPS2 in prostate cancer cell lines induced apoptosis within 48 h, which indicates that REPS2 may play a role in the life-death balance of the cell. To elucidate cellular functions of REPS2, proteins were identified that bind REPS2. A large fragment of the NF-ÎºB subunit p65 (RELA) was found to bind REPS2. This protein p65 is inactive in ADPC but active in AIPC, and might cause cell survival through inhibition of apoptotic cell death. Two other protein sequences that were found to bind REPS2 represent parts of TRAF4 and STAT6. Interestingly, these two proteins, like p65, are implicated in control of some aspects of the NF-ÎºB pathway. Taken together, the results point to a putative inhibitory effect of REPS2 on NF-kB signalling and prostate cancer cell survival.
|Keywords||NF-kappaB, REPS2, STAT6, TRAF4, apoptosis, cell survival, mammalian two-hybrid system, prostate cancer, protein-protein interaction, signal transduction, yeast two-hybrid system|
Penninkhof, T.F.E.. (2005, August 31). Interaction of REPS2 with NF-kappaB in Prostate Cancer Cells. Retrieved from http://hdl.handle.net/1765/6905