title: Down-regulated expression of apoptosis-associated genes APIP and UACA             in non-small cell lung carcinoma.
abstract: The Apaf-1 interacting protein (APIP) and the uveal autoantigen with coiled             coil domains and ankyrin repeats (UACA) belong to endogenous regulators of the             apoptosome apparatus, but their role in tumourigenesis and progression of non-small             cell lung carcinoma (NSCLC) is not known. Previous studies demonstrated that APIP             inhibits the apoptosome-mediated procaspase-9 activation while UACA induces translocation             of Apaf-1 from the cytoplasm into the nucleus. Here, we report for the first time             that the expression of APIP and UACA genes is down-regulated on the level of both             mRNA and protein in NSCLC cells and tumours. In particular, the expression of             APIP protein was strikingly decreased and the expression of UACA mRNA and protein             was frequently down-regulated in NSCLC tumours of different histopathological             types. Moreover, stage IA NSCLC tumours showed significantly lower expression             of UACA mRNA compared to higher stage tumours. The weak increase of both APIP             and UACA mRNA levels in the 5-aza-2'-deoxycytidine-treated NSCLC cells indicates             that mechanisms other than DNA methylation are involved in the regulation of APIP             and UACA gene expression in these cancer cells. Taken together, the down-regulation             of APIP and UACA expression suggests that the threshold to activate the apoptosome             apparatus may be decreased in NSCLC cells due to the lack of APIP-mediated suppression             and UACA-assisted Apaf-1 nuclear entry. Moreover, the loss of UACA-assisted Apaf-1             nuclear translocation may underlie the failure of DNA damage checkpoint activation             in NSCLC cells leading to their genomic instability.
authors.affiliation: Laboratories of Molecular and Cell Biology, University Hospital                     Bulovka and 3rd Faculty of Medicine, Charles University in Prague, Prague,                     Czech Republic.
authors.forename: Erika
authors.initials: E
authors.lastname: Moravcikova
authors.forename: Evzen
authors.initials: E
authors.lastname: Krepela
authors.forename: Jan
authors.initials: J
authors.lastname: Prochazka
authors.forename: Ilona
authors.initials: I
authors.lastname: Rousalova
authors.forename: Jan
authors.initials: J
authors.lastname: Cermak
authors.forename: Kamila
authors.initials: K
authors.lastname: Benkova
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic
chemical_list: C573917:APIP protein, human; D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; C422446:UACA antigen