Abstract
p63
, a member of the
p53
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.
