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- Title
Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.
- Authors
Koga, F; Kawakami, S; Kumagai, J; Takizawa, T; Ando, N; Arai, G; Kageyama, Y; Kihara, K
- Abstract
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.
- Subjects
PROTEIN metabolism; BLADDER tumors; REVERSE transcriptase polymerase chain reaction; CANCER cell culture; PROTEINS; RESEARCH; WESTERN immunoblotting; ONCOGENES; RESEARCH methodology; CYTOSKELETAL proteins; RNA; EVALUATION research; DNA probes; NUCLEOTIDES; COMPARATIVE studies; PHOSPHOPROTEINS; DNA-binding proteins; MEMBRANE proteins; TRANSCRIPTION factors; POLYMERASE chain reaction; PHENOTYPES
- Publication
British Journal of Cancer, 2003, Vol 88, Issue 5, p740
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6600764