Differentially expressed downstream genes in cells with normal or mutated p53.
Mutations in p53 gene could lead to loss of function, negative complementation, or to gain-of-oncogenic functions, thus leading to the increase of tumorigenicity and invasiveness of cancer. This study focused on cancer-related p53 mutants, including A138T, C141Y, RI58L, G245C, and R248Q. Using a modified differential display technique, response profiles of plasmid-expressed wild-type as well as mutated p53, in comparison to p53-null cells, are being established. These profiles can help our understanding of p53 involvement in cancer, leading to accurate diagnosis, treatment, and prognostic analysis by: 1) comprehensive knowledge of p53 network gene expression profiles; 2) finding the most significant gene expression profiles of p53 mutants; 3) revealing genes that only respond to p53 mutants (gain of function). Our results showed significant differences in the expression patterns among p53-null. wild-type p53, and p53 mutants A138T, C141Y, R158L, G245C, and R248Q samples. We also report here the first found p53 mutant-triggered alternative splicing.
Department of Biotechnology, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway.
Hao
H
Xu
M Raafat
MR
El-Gewely
D017398:Alternative Splicing / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics; D017421:Sequence Analysis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured