TY - JOUR
T1 - Loss of p63 expression is associated with tumor proaression in bladder cancer
AU - Urist, Marshall J.
AU - Di Como, Charles J.
AU - Lu, Ming Lan
AU - Charytonowicz, Elizabeth
AU - Verbel, David
AU - Crum, Christopher P.
AU - Ince, Tan A.
AU - McKeon, Frank D.
AU - Cordon-Cardo, Carlos
N1 - Funding Information:
Suported by the Leukemia and Lymphoma Society (special fellowship no. 3956-01 to C. J. D. ) and the National Institutes of Health (grants CA-87497, CA-47179, and DK-47650 to C. C.-C. ).
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)64396-9
DO - 10.1016/S0002-9440(10)64396-9
M3 - Article
C2 - 12368193
AN - SCOPUS:0036791603
VL - 161
SP - 1199
EP - 1206
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -