PURPOSE: RBM5 is an RNA binding protein that has the ability to modulate apoptosis. Overerxpression of RBM5 either sensitizes cells to certain apoptotic stimuli or induces apoptosis, outcomes likely related to RBM5 expression levels. We previously demonstrated that Jurkat cells overexpressing RBM5 had increased sensitivity to apoptosis mediated by tumour necrosis factor alpha (TNF-alpha) and the TNF receptor apoptosis inducing ligand (TRAIL). To investigate the mechanism behind this sensitization process, we examined the expression of key apoptosis associated genes in RBM5 overexpressing cells.
METHODS: A real-time polymerase chain reaction (PCR)-based pathway-focused gene expression profiling system was used. Simultaneous expression of 84 apoptosis-associated genes was examined. Quantitative determination of protein expression was examined using an enzyme-linked immunosorbent assay (ELISA).
RESULTS: In three separate assays, upregulation of RBM5 mRNA was positively correlated with the expression of TNF-alpha mRNA. Increased production of secreted TNF-alpha protein was detected by ELISA. These results suggest that the increased sensitivity of RBM5 overexpressing cancer cells to TNF-alpha-mediated apoptosis is contributed to by elevated levels of endogenous TNF-alpha ligand in the culture supernatant.
CONCLUSION: Based on these findings, we speculate that cancer cells expressing relatively high levels of endogenous RBM5 may be more susceptible to certain apoptogenic chemotherapeutic drugs, particularly those functioning via the TNF-alpha signaling pathway.
CLINICAL IMPLICATIONS: RBM5 might be a new target for the cancer chemotherapy.
DISCLOSURE: Ke Wang, No Financial Disclosure Information; No Product/Research Disclosure Information