TY - JOUR
T1 - The p53-homologue p63 may promote thyroid cancer progression
AU - Malaguarnera, Roberta
AU - Mandarino, Angelo
AU - Mazzon, Emanuela
AU - Vella, Veronica
AU - Gangemi, Piero
AU - Vancheri, Carlo
AU - Vigneri, Paolo
AU - Aloisi, Alessandra
AU - Vigneri, Riccardo
AU - Frasca, Francesco
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
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U2 - 10.1677/erc.1.00968
DO - 10.1677/erc.1.00968
M3 - Article
C2 - 16322335
AN - SCOPUS:29144478507
VL - 12
SP - 953
EP - 971
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 4
ER -