D'Avenia, Morena (2009) air: a new, un-mapped, sequence that modulates apoptosis. [Tesi di dottorato] (Inedito)

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Abstract

air (apoptosis-induced regulator) was previously identified as a pro-apoptotic transcript whose expression was repressed by NF-kB/Rel activity in the human leukemia cell line Jurkat (Turco MC et al., 2007). Oddly, air sequence was missing in human genome databases. This PhD Thesis shows that air sequence is detectable by PCR and Southern blot in human healthy donors (HHD) leucocytes and carcinoma cell lines, providing the first definitive evidence of air gene presence in human genome. Moreover, in the chimpanzee trace-WGS database, air homologous sequences were found. Then, air flanking regions, on genomic DNA, were isolated to allow a probe synthesis, suited to perform a FISH assay. In addition, bioinformatics studies about air structure and function prediction were performed. Furthermore, this thesis shows that air expression is induced in tumor cell lines by a naturally occurring ROS-inducing compound, phenethyl isothiocyanate (PEITC), a potential dietary cancer chemopreventive agent. Since PEITC inhibits NF-kB activation, air induction by this agent is consistent with the suppressive effect of NF-kB on air expression. This finding contributes a new clue to the role of NF-kB in regulating oxidative stress- induced pro-apoptotic genes and identifies a novel potential tool for enhancing cancer response to treatment.

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