| Abstract: |
p63, a member of thep53 gene family, encodes multiple proteins that may either transactivate p53 responsive genes (TAp63) or act as a dominant-negative factor toward p53 and p73 (ΔNp63). p63 is expressed in many epithelial compartments and p63-/- mice fail to develop skin, prostate, and mammary glands among other defects. It has been previously shown that p63 is expressed in normal urothelium. This study reports that p63 is regulated in bladder carcinogenesis and that p63 expression is lost in most invasive cancers whereas papillary superficial tumors maintain p63 expression. Examination of bladder carcinoma cell lines reveals that certain lines derived from invasive carcinomas maintain expression of ΔNp63, as demonstrated by both immunoblotting and confirmed by isoform-specific quantitative reverse transcriptase-polymerase chain reaction. Another novel finding reported in this study is the fact that p63-/- mice develop a bladder mucosa epithelial layer yet fail to complete uroepithelial differentiation, producing a nontransitional default cuboidal epithelium. These data indicate that in contrast to the skin and prostate, p63 is not required for formation of a bladder epithelium but is indispensable for the specific differentiation of a transitional urothelium. |
| Keywords: |
controlled study; human tissue; protein expression; human cell; dna-binding proteins; animals; mice; mice, knockout; reverse transcription polymerase chain reaction; membrane proteins; cell differentiation; cancer cell culture; tumor cells, cultured; bladder cancer; urinary bladder neoplasms; skin; urothelium; gene expression regulation, neoplastic; prostate; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; quantitative analysis; disease progression; tumor suppressor proteins; urinary bladder; immunoblotting; phosphoproteins; base sequence; gene control; invasive carcinoma; protein p63; neoplasm invasiveness; trans-activators; papilloma; dna primers; tumor growth; carcinoma, transitional cell; bladder carcinogenesis; genes, tumor suppressor; urinary tract; bladder mucosa; superficial cancer; bladder epithelium; humans; human; priority journal; article
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