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Departments of Pathology [B-J. P., J-H. P., S-G. Chi.] and Urology [Se-J. L., J. I. K., Su-J. L., C-H. L., S-G. Cha.], School of Medicine, Kyung Hee University, Seoul 130-701, Korea
p63, a recently identified member of the
p53 gene family, encodes multiple products with
transactivating, death-inducing, and dominant-negative activities. To
explore the penetrance of p63 in bladder carcinogenesis,
we performed expression and mutation analyses of two major isotypes,
TAp63 and 
Np63, in 63
bladder specimens. In 12 normal tissues, TAp63 was
expressed at an easily detectable level whereas
Np63 was absent or extremely low.
While none of 47 carcinomas showed allelic deletion of the gene, marked
reduction of TAp63 and abnormal overexpression of
Np63 were found in 25 (53.2%) and 30
(63.8%) carcinomas, respectively. Tumor-specific alteration of
TAp63 and Np63
expression was identified in two and three of six matched sets,
respectively. In addition, reduced expression of TAp63
showed a correlation with tumor stage and grade. Abnormal expression of
TAp63 or Np63 isoform
was also observed in three of four cell lines, and treatment with
5-Aza-2'-deoxycytidine led to up- or down-regulation of
TAp63 and/or Np63
expression, suggesting that the promoters of both isoforms might be
affected by DNA methylation, but not in a reciprocal fashion. No
sequence alteration of p63 was identified in 47
carcinomas whereas 17 (34.8%) of these showed p53
mutations, and no association between p63 expression and
the mutational status of p53 or expression of
p21Waf1, MDM2, and
14–3-3
was recognized. Our data suggest that altered
expression of p63 is a frequent event in bladder
carcinogenesis and might contribute to the progression of bladder
tumors, possibly via the mechanism(s) distinct from the p53 pathway.
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 U. M. Moll The Role of p63 and p73 in Tumor Formation and Progression: Coming of Age Toward Clinical Usefulness: Commentary re: F. Koga et al., Impaired p63 Expression Associates with Poor Prognosis and Uroplakin III Expression in Invasive Urothelial Carcinoma of the Bladder. Clin. Cancer Res., 9: 5501-5507, 2003, and P. Puig et al., p73 Expression in Human Normal and Tumor Tissues: Loss of p73{alpha} Expression Is Associated with Tumor Progression in Bladder Cancer. Clin. Cancer Res., 9: 5642-5651, 2003. Clin. Cancer Res., November 15, 2003; 9(15): 5437 - 5441. [Full Text] [PDF]
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F. Koga, S. Kawakami, Y. Fujii, K. Saito, Y. Ohtsuka, A. Iwai, N. Ando, T. Takizawa, Y. Kageyama, and K. Kihara Impaired p63 Expression Associates with Poor Prognosis and Uroplakin III Expression in Invasive Urothelial Carcinoma of the Bladder Clin. Cancer Res., November 15, 2003; 9(15): 5501 - 5507. [Abstract] [Full Text] [PDF]
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P. P. Massion, P. M. Taflan, S. M. Jamshedur Rahman, P. Yildiz, Y. Shyr, M. E. Edgerton, M. D. Westfall, J. R. Roberts, J. A. Pietenpol, D. P. Carbone, et al. Significance of p63 Amplification and Overexpression in Lung Cancer Development and Prognosis Cancer Res., November 1, 2003; 63(21): 7113 - 7121. [Abstract] [Full Text] [PDF]
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G. Wu, S. Nomoto, M. O. Hoque, T. Dracheva, M. Osada, C.-C. R. Lee, S. M. Dong, Z. Guo, N. Benoit, Y. Cohen, et al. {Delta}Np63{alpha} and TAp63{alpha} Regulate Transcription of Genes with Distinct Biological Functions in Cancer and Development Cancer Res., May 15, 2003; 63(10): 2351 - 2357. [Abstract] [Full Text] [PDF]
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 M. J. Urist, C. J. Di Como, M.-L. Lu, E. Charytonowicz, D. Verbel, C. P. Crum, T. A. Ince, F. D. McKeon, and C. Cordon-Cardo Loss of p63 Expression Is Associated with Tumor Progression in Bladder Cancer Am. J. Pathol., October 1, 2002; 161(4): 1199 - 1206. [Abstract] [Full Text] [PDF]
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 A. I. Zaika, N. Slade, S. H. Erster, C. Sansome, T. W. Joseph, M. Pearl, E. Chalas, and U. M. Moll {Delta}Np73, A Dominant-Negative Inhibitor of Wild-type p53 and TAp73, Is Up-regulated in Human Tumors J. Exp. Med., September 16, 2002; 196(6): 765 - 780. [Abstract] [Full Text] [PDF]
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S. Strano, G. Fontemaggi, A. Costanzo, M. G. Rizzo, O. Monti, A. Baccarini, G. Del Sal, M. Levrero, A. Sacchi, M. Oren, et al. Physical Interaction with Human Tumor-derived p53 Mutants Inhibits p63 Activities J. Biol. Chem., May 17, 2002; 277(21): 18817 - 18826. [Abstract] [Full Text] [PDF]
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H. Nishi, M. Senoo, K. H. Nishi, B. Murphy, T. Rikiyama, Y. Matsumura, S. Habu, and A. C. Johnson p53 Homologue p63 Represses Epidermal Growth Factor Receptor Expression J. Biol. Chem., November 2, 2001; 276(45): 41717 - 41724. [Abstract] [Full Text] [PDF]
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C. Gaiddon, M. Lokshin, J. Ahn, T. Zhang, and C. Prives A Subset of Tumor-Derived Mutant Forms of p53 Down-Regulate p63 and p73 through a Direct Interaction with the p53 Core Domain Mol. Cell. Biol., March 1, 2001; 21(5): 1874 - 1887. [Abstract] [Full Text]
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 E. A. Ratovitski, M. Patturajan, K. Hibi, B. Trink, K. Yamaguchi, and D. Sidransky p53 associates with and targets Delta Np63 into a protein degradation pathway PNAS, February 13, 2001; 98(4): 1817 - 1822. [Abstract] [Full Text] [PDF]
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