Loss of p63 expression is associated with tumor proaression in bladder cancer

Marshall J. Urist, Charles J. Di Como, Ming Lan Lu, Elizabeth Charytonowicz, David Verbel, Christopher P. Crum, Tan Ince, Frank D. McKeon, Carlos Cordon-Cardo

Research output: Contribution to journalArticle

210 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1199-1206
Number of pages8
JournalAmerican Journal of Pathology
Volume161
Issue number4
StatePublished - Oct 1 2002
Externally publishedYes

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Urinary Bladder Neoplasms
Urinary Bladder
Urothelium
Prostate
Neoplasms
Epithelium
Carcinoma
Skin
p53 Genes
Human Mammary Glands
Reverse Transcriptase Polymerase Chain Reaction
Immunoblotting
Protein Isoforms
Carcinogenesis
Mucous Membrane
Cell Line
Genes
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Urist, M. J., Di Como, C. J., Lu, M. L., Charytonowicz, E., Verbel, D., Crum, C. P., ... Cordon-Cardo, C. (2002). Loss of p63 expression is associated with tumor proaression in bladder cancer. American Journal of Pathology, 161(4), 1199-1206.

Loss of p63 expression is associated with tumor proaression in bladder cancer. / Urist, Marshall J.; Di Como, Charles J.; Lu, Ming Lan; Charytonowicz, Elizabeth; Verbel, David; Crum, Christopher P.; Ince, Tan; McKeon, Frank D.; Cordon-Cardo, Carlos.

In: American Journal of Pathology, Vol. 161, No. 4, 01.10.2002, p. 1199-1206.

Research output: Contribution to journalArticle

Urist, MJ, Di Como, CJ, Lu, ML, Charytonowicz, E, Verbel, D, Crum, CP, Ince, T, McKeon, FD & Cordon-Cardo, C 2002, 'Loss of p63 expression is associated with tumor proaression in bladder cancer', American Journal of Pathology, vol. 161, no. 4, pp. 1199-1206.
Urist MJ, Di Como CJ, Lu ML, Charytonowicz E, Verbel D, Crum CP et al. Loss of p63 expression is associated with tumor proaression in bladder cancer. American Journal of Pathology. 2002 Oct 1;161(4):1199-1206.
Urist, Marshall J. ; Di Como, Charles J. ; Lu, Ming Lan ; Charytonowicz, Elizabeth ; Verbel, David ; Crum, Christopher P. ; Ince, Tan ; McKeon, Frank D. ; Cordon-Cardo, Carlos. / Loss of p63 expression is associated with tumor proaression in bladder cancer. In: American Journal of Pathology. 2002 ; Vol. 161, No. 4. pp. 1199-1206.
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