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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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 R Malaguarnera, V Vella, R Vigneri, and F Frasca p53 family proteins in thyroid cancer Endocr. Relat. Cancer, March 1, 2007; 14(1): 43 - 60. [Abstract] [Full Text] [PDF]
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M. I. Koster, S.-L. Lu, L. D. White, X.-J. Wang, and D. R. Roop Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression. Cancer Res., April 15, 2006; 66(8): 3981 - 3986. [Abstract] [Full Text] [PDF]
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E. S. Helton, J. Zhu, and X. Chen The Unique NH2-terminally Deleted ({Delta}N) Residues, the PXXP Motif, and the PPXY Motif Are Required for the Transcriptional Activity of the {Delta}N Variant of p63 J. Biol. Chem., February 3, 2006; 281(5): 2533 - 2542. [Abstract] [Full Text] [PDF]
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R. Malaguarnera, A. Mandarino, E. Mazzon, V. Vella, P. Gangemi, C. Vancheri, P. Vigneri, A. Aloisi, R. Vigneri, and F. Frasca The p53-homologue p63 may promote thyroid cancer progression Endocr. Relat. Cancer, December 1, 2005; 12(4): 953 - 971. [Abstract] [Full Text] [PDF]
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 D.-Y. Wang, C.-C. Cheng, M.-H. Kao, Y.-J. Hsueh, D. H. K. Ma, and J.-K. Chen Regulation of Limbal Keratinocyte Proliferation and Differentiation by TAp63 and {Delta}Np63 Transcription Factors Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3102 - 3108. [Abstract] [Full Text] [PDF]
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 H. Ying, D. L. F. Chang, H. Zheng, F. McKeon, and Z.-X. J. Xiao DNA-Binding and Transactivation Activities Are Essential for TAp63 Protein Degradation Mol. Cell. Biol., July 15, 2005; 25(14): 6154 - 6164. [Abstract] [Full Text] [PDF]
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 J. M. A. Moreira, G. Ohlsson, F. E. Rank, and J. E. Celis Down-regulation of the Tumor Suppressor Protein 14-3-3{sigma} Is a Sporadic Event in Cancer of the Breast Mol. Cell. Proteomics, April 1, 2005; 4(4): 555 - 569. [Abstract] [Full Text] [PDF]
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C. E. Barbieri, C. A. Perez, K. N. Johnson, K. A. Ely, D. Billheimer, and J. A. Pietenpol IGFBP-3 Is a Direct Target of Transcriptional Regulation by {Delta}Np63{alpha} in Squamous Epithelium Cancer Res., March 15, 2005; 65(6): 2314 - 2320. [Abstract] [Full Text] [PDF]
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 P. P. Massion, P. M. Taflan, Y. Shyr, S. M. J. Rahman, P. Yildiz, B. Shakthour, M. E. Edgerton, M. Ninan, J. J. Andersen, and A. L. Gonzalez Early Involvement of the Phosphatidylinositol 3-Kinase/Akt Pathway in Lung Cancer Progression Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1088 - 1094. [Abstract] [Full Text] [PDF]
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U. M. Moll and N. Slade p63 and p73: Roles in Development and Tumor Formation Mol. Cancer Res., July 1, 2004; 2(7): 371 - 386. [Abstract] [Full Text] [PDF]
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 M. D. Westfall and J. A. Pietenpol p63: molecular complexity in development and cancer Carcinogenesis, June 1, 2004; 25(6): 857 - 864. [Abstract] [Full Text] [PDF]
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J. M. A. Moreira, P. Gromov, and J. E. Celis Expression of the Tumor Suppressor Protein 14-3-3{sigma} Is Down-regulated in Invasive Transitional Cell Carcinomas of the Urinary Bladder Undergoing Epithelial-to-Mesenchymal Transition Mol. Cell. Proteomics, April 1, 2004; 3(4): 410 - 419. [Abstract] [Full Text] [PDF]
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K. Onel and C. Cordon-Cardo MDM2 and Prognosis Mol. Cancer Res., January 1, 2004; 2(1): 1 - 8. [Abstract] [Full Text] [PDF]
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C. E. Barbieri, C. E. Barton, and J. A. Pietenpol {Delta}Np63{alpha} Expression Is Regulated by the Phosphoinositide 3-Kinase Pathway J. Biol. Chem., December 19, 2003; 278(51): 51408 - 51414. [Abstract] [Full Text] [PDF]
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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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K. Hibi, S.-i. Fujitake, T. Takase, Y. Kodera, K. Ito, S. Akiyama, M. Shirane, and A. Nakao Identification of S100A2 as a Target of the {Delta}Np63 Oncogenic Pathway Clin. Cancer Res., September 15, 2003; 9(11): 4282 - 4285. [Abstract] [Full Text] [PDF]
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 C. Langner, M. Ratschek, O. Tsybrovskyy, L. Schips, and R. Zigeuner P63 Immunoreactivity Distinguishes Upper Urinary Tract Transitional-cell Carcinoma and Renal-cell Carcinoma Even in Poorly Differentiated Tumors J. Histochem. Cytochem., August 1, 2003; 51(8): 1097 - 1099. [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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