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Endocrine-Related Cancer 12 (4) 953-971    DOI: 10.1677/erc.1.00968
Copyright © 2005 by the Society for Endocrinology.
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The p53-homologue p63 may promote thyroid cancer progression

Roberta Malaguarnera*, Angelo Mandarino*, Emanuela Mazzon1, Veronica Vella, Piero Gangemi2, Carlo Vancheri3, Paolo Vigneri4, Alessandra Aloisi, Riccardo Vigneri and Francesco Frasca

Dipartimento di Medicina Interna e di Medicina Specialistica — Endocrinologia, Università di Catania, 95123 Catania, Italy
1 Centro di Biomorfologia, Università di Messina, 98122 Messina, Italy
2 Servizio di Anatomia Patologica, Ospedale Vittorio Emanuele, 95124 Catania, Italy
3 Malattie Apparato Respiratorio, Università di Catania, 95123 Catania, Italy
4 Dipartimento di Scienze Biomediche, Università di Catania, 95124 Catania, Italy

(Requests for offprints should be addressed to F Frasca; Email: f.frasca{at}unict.it)

Inactivation of p53 and p73 is known to promote thyroid cancer progression. We now describe p63 expression and function in human thyroid cancer. TAp63{alpha} is expressed in most thyroid cancer specimens and cell lines, but not in normal thyrocytes. However, in thyroid cancer cells TAp63{alpha} fails to induce the target genes (p21Cip1, Bax, MDM2) and, as a consequence, cell cycle arrest and apoptosis occur. Moreover, TAp63{alpha} antagonizes the effect of p53 on target genes, cell viability and foci formation, and p63 gene silencing by small interfering (si) RNA results in improved p53 activity. This unusual effect of TAp63{alpha} depends on the protein C-terminus, since TAp63ß and TAp63{gamma} isoforms, which have a different arrangement of their C-terminus, are still able to induce the target genes and to exert tumour-restraining effects in thyroid cancer cells. Our data outline the existence of a complex network among p53 family members, where TAp63{alpha} may promote thyroid tumour progression by inactivating the tumour suppressor activity of p53.




This article has been cited by other articles:


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 Mol Cancer ResHome page
R. Malaguarnera, V. Vella, G. Pandini, M. Sanfilippo, V. Pezzino, R. Vigneri, and F. Frasca
TAp73{alpha} Increases p53 Tumor Suppressor Activity in Thyroid Cancer Cells via the Inhibition of Mdm2-Mediated Degradation
Mol. Cancer Res., January 1, 2008; 6(1): 64 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
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]

Home page
 Cancer Res.Home page
F. Frasca, A. Rustighi, R. Malaguarnera, S. Altamura, P. Vigneri, G. Del Sal, V. Giancotti, V. Pezzino, R. Vigneri, and G. Manfioletti
HMGA1 Inhibits the Function of p53 Family Members in Thyroid Cancer Cells.
Cancer Res., March 15, 2006; 66(6): 2980 - 2989.
[Abstract] [Full Text] [PDF]


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