The p53-homologue p63 may promote thyroid cancer progression

Roberta Malaguarnera, Angelo Mandarino, Emanuela Mazzon, Veronica Vella, Piero Gangemi, Carlo Vancheri, Paolo Vigneri, Alessandra Aloisi, Riccardo Vigneri, Francesco Frasca

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Abstract

Inactivation of p53 and p73 is known to promote thyroid cancer progression. We now describe p63 expression and function in human thyroid cancer. TAp63α is expressed in most thyroid cancer specimens and cell lines, but not in normal thyrocytes. However, in thyroid cancer cells TAp63α fails to induce the target genes (p21Cip1, Bax, MDM2) and, as a consequence, cell cycle arrest and apoptosis occur. Moreover, TAp63α 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 TAp63α depends on the protein C-terminus, since TAp63β and TAp63γ 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 TAp63α may promote thyroid tumour progression by inactivating the tumour suppressor activity of p53.

Original languageEnglish
Pages (from-to)953-971
Number of pages19
JournalEndocrine-Related Cancer
Volume12
Issue number4
DOIs
Publication statusPublished - Dec 2005

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ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Malaguarnera, R., Mandarino, A., Mazzon, E., Vella, V., Gangemi, P., Vancheri, C., Vigneri, P., Aloisi, A., Vigneri, R., & Frasca, F. (2005). The p53-homologue p63 may promote thyroid cancer progression. Endocrine-Related Cancer, 12(4), 953-971. https://doi.org/10.1677/erc.1.00968