A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.
Journal article, 2004
Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.
Genes
Messenger
Sequence Homology
genetics
Human
Tumor Suppressor Proteins
Sequence Alignment
Polymerase Chain Reaction
RNA
Neuroblastoma
Animals
genetics
genetics
genetics
Chromosome Mapping
genetics
Tumor Suppressor
Base Sequence
Chromosomes
Mutation
genetics
Molecular Sequence Data
Apoptosis Regulatory Proteins
Tumor Suppressor Protein p53
Humans
Promoter Regions (Genetics)
DNA Primers
Pair 1
Amino Acid Sequence
Amino Acid
genetics
Author
Cecilia Krona
University of Gothenburg
Katarina Ejeskär
University of Gothenburg
Helena Carén
University of Gothenburg
Frida Abel
University of Gothenburg
Rose-Marie Sjöberg
University of Gothenburg
Tommy Martinsson
University of Gothenburg
British Journal of Cancer
0007-0920 (ISSN) 1532-1827 (eISSN)
Vol. 91 6 1119-30Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1038/sj.bjc.6602083