By systematically profiling expression of apoptosis pathway proteins with respect to histological sub-types of non-small cell lung cancer in human lung cancer cell lines, we have been able to identify specific patterns of defects in the expression and regulation of apoptosis pathways in lung cancer cells. Also, these apoptosis pathway differences between lung cancer cell types may suggest specific intra-cellular road-blocks which are critical to overcome in order to cause cell death in the lung cancer cell. To that effect, we have performed studies which show that knock-down of specific anti-apoptosis molecules can successfully render a previously apoptosis-resistant lung cancer cell more susceptible to apoptosis induction and result in cancer cell death. Our goal to elucidate the mechanisms responsible for the differences in apoptosis expression in lung cancer sub-types have recently led us to identify a specific microRNA which is involved in the regulation of the translational expression of the most potent IAP (inhibitor of apoptosis). Furthermore, we have identified the putative binding site on the messenger RNA for this microRNA and we are in the process of determining the precise nucleic acid base(s) necessary for microRNA-messenger RNA interaction. The actions of this particular microRNA can down-regulate the expression of IAP, therefore rendering the cancer cell more susceptible to cell-death induction by other pro-apoptosis agents. Our next step is to determine in vivo, using small animal models, the activity of exogenous supplied microRNA to lung cancer tumors.
NIH ExPorter
NIH ExPorter