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Publication : Loss of p63 expression is associated with tumor progression in bladder cancer.

First Author  Urist MJ Year  2002
Journal  Am J Pathol Volume  161
Issue  4 Pages  1199-206
PubMed ID  12368193 Mgi Jnum  J:79341
Mgi Id  MGI:2387880 Doi  10.1016/S0002-9440(10)64396-9
Citation  Urist MJ, et al. (2002) Loss of p63 Expression Is Associated with Tumor Progression in Bladder Cancer. Am J Pathol 161(4):1199-206
abstractText  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 (DeltaNp63). 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 DeltaNp63, 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.
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