title: Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma tumours with unfavourable biology.
abstract: It has been proposed that a lack of apoptosis plays an important role in neuroblastoma (NB) progression. We therefore screened cDNA array filters, including 198 apoptotic genes, in order to identify mRNA transcripts that are differentially expressed in tumours with unfavourable versus favourable biology. Twenty-one genes were analysed further using real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Significantly lower levels of DNCL1 (PIN; P(c)(corrected) = 0.0054) and NTRK1 (TrkA; P(c) = 0.039) were found in NB tumours with unfavourable biology. In addition, BID, BCL2, APAF1, CASP2, CASP3 and CASP9 were found to be preferentially expressed in tumours with favourable biology, whereas CDKN1A (p21), IL2RA, and MCL1, were found to be preferentially expressed in NB tumours with unfavourable biology. In conclusion, mRNA levels of transcripts encoding pro-apoptotic mediators of the mitochondrial apoptotic pathway were found to be expressed to a lower extent in tumours with unfavourable biology. Our data also suggest that the mitochondrial pathway is suppressed in advanced stages of NB tumours, due to an imbalance between anti-apoptotic and pro-apoptotic mediators which is a finding that may have therapeutic significance.
authors.affiliation: Department of Clinical Genetics, Gothenburg University, Sahlgrenska University Hospital/East, S-416 85 Gothenburg, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Abel
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Sjöberg
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000473:pathology*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D012322:RNA Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D018076:DNA, Complementary; D012322:RNA Precursors; D012333:RNA, Messenger