Battista S, Martelli M L, Fedele M, Chiappetta G, Trapasso F, De Vita G, Battaglia C, Santoro M, Viglietto G, Fagin J A
Istituto Nazionale dei Tumori, Fondazione Pascale, Napoli-Italia.
Oncogene. 1995 Nov 16;11(10):2029-37.
p53 is the gene most frequently found mutated in human neoplasias. In the majority of tumors, p53 mutations contribute to the progression towards stages of increasing malignancy with the appearance of an undifferentiated phenotype. Also in thyroid cancerogenesis, p53 mutations correlate with the loss of the differentiated phenotype. The results presented here, suggest a direct involvement of p53 in the molecular mechanisms regulating cellular differentiation in thyroid since a mutated p53 gene markedly affects the growth potential and differentiated functions of the rat thyroid cell line PC Cl 3. Blockage in the expression of the PAX-8 transcription factor seems to be a key event in the loss of thyroid differentiated functions induced by the mutated p53 gene. Thyroid cells carrying a mutated p53 gene did not form colonies in soft agar or tumors in athymic mice, suggesting that a mutation of the p53 gene is not sufficient for the induction of the malignant phenotype and probably a cooperation with other oncogenes is necessary to accomplish full malignancy. No effect on either growth or differentiation of thyroid cells was exerted either by overexpression of the wild-type p53 gene, or by the vector alone.
p53是人类肿瘤中最常发生突变的基因。在大多数肿瘤中，p53突变会随着未分化表型的出现，促使肿瘤向恶性程度增加的阶段发展。在甲状腺癌发生过程中，p53突变也与分化表型的丧失相关。本文给出的结果表明，p53直接参与了调节甲状腺细胞分化的分子机制，因为突变的p53基因会显著影响大鼠甲状腺细胞系PC Cl 3的生长潜能和分化功能。PAX - 8转录因子表达的阻断似乎是突变的p53基因诱导甲状腺分化功能丧失的关键事件。携带突变p53基因的甲状腺细胞在软琼脂中不形成集落，在无胸腺小鼠中也不形成肿瘤，这表明p53基因的突变不足以诱导恶性表型，可能需要与其他癌基因协同作用才能实现完全恶性转化。野生型p53基因的过表达或单独的载体对甲状腺细胞的生长或分化均无影响。
