NSP 5a3a: a potential novel cancer target in head and neck carcinoma.
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/5554
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AbstractNSP 5a3a along with three other distinct though similar splice variants were initially identified corresponding to locus HCMOGT-1 on chromosome 17p11.2 . Secondary structure analysis of the novel structural protein (NSP) isoforms revealed similarity to Spectrin like proteins containing coiled coil domains . The NSP 5a3a isoform had been found to be highly expressed in-vitro in particular cancer cell lines while very low to un-detectable levels in normal body tissues . Subsequent investigation of this isoform revealed its novel interaction with B23 , a multifunctional nucleolar protein involved in ribosome biogenesis, rRNA transcription, mitosis, cell growth control, and apoptosis . Subsequent investigation, elucidated NSP 5a3a's potential involvement in cellular processes such as ribosome biogenesis and rRNA processing by validating NSP 5a3a's novel interaction with B23 and ribonuclear protein hnRNP-L possibly implicating NSP 5a3a's involvement in cellular activities such as RNA metabolism and processing . In this preliminary investigation, we wanted to observe the effect that over-expressing NSP 5a3a may have on cell cycle and its potential application in cancer treatment in aggressive cancers such as head and neck carcinomas. Over-expressed NSP 5a3a in HN30 cells induced a significant degree of apoptosis, an average of a 10.85 fold increase compared to controls 3 days post-transfection. This effect was more significant then the apoptosis observed between Fadu cells over-expressing NSP 5a3a and its controls. Though, the apoptosis induced in the WI38 control cell line showed an average of a 13.2 fold increase between treated and controls comparable to the HN30 cell line 3 days post-transfection. Molecular analysis indentified a novel p73 dependent mechanism independent of p53 and caspase 3 activity through which NSP 5a3a is inducing apoptosis. We propose NSP 5a3a as a potential therapeutic target for site directed cancer treatment in perhaps certain head and neck carcinomas by induction of apoptosis.
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