The p53-homologue p63 may promote thyroid cancer progression.
Inactivation of p53 and p73 is known to promote thyroid cancer progression. We now describe p63 expression and function in human thyroid cancer. TAp63alpha is expressed in most thyroid cancer specimens and cell lines, but not in normal thyrocytes. However, in thyroid cancer cells TAp63alpha fails to induce the target genes (p21Cip1, Bax, MDM2) and, as a consequence, cell cycle arrest and apoptosis occur. Moreover, TAp63alpha 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 TAp63alpha depends on the protein C-terminus, since TAp63beta and TAp63gamma 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 TAp63alpha may promote thyroid tumour progression by inactivating the tumour suppressor activity of p53.
Malaguarnera
Roberta
R
Dipartimento di Medicina Interna e di Medicina Specialistica - Endocrinologia, Università di Catania, Italy.
Mandarino
Angelo
A
Mazzon
Emanuela
E
Vella
Veronica
V
Gangemi
Piero
P
Vancheri
Carlo
C
Vigneri
Paolo
P
Aloisi
Alessandra
A
Vigneri
Riccardo
R
Frasca
Francesco
F
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins