Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.
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.
Koga
F
F
Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.
Kawakami
S
S
Kumagai
J
J
Takizawa
T
T
Ando
N
N
Arai
G
G
Kageyama
Y
Y
Kihara
K
K
D001483:Base Sequence; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin
C081876:CKAP4 protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin