Genomic instability and apoptosis are frequent in p53 deficient young mice
Genomic instability and apoptosis are frequent in p53 deficient young mice
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DOI：
10.1038/sj.onc.1201482
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发表时间：
1997-09-11
期刊：
影响因子：
8
通讯作者：
Mai, SB
中科院分区：
文献类型：
--
作者：
Fukasawa, K;Wiener, F;Mai, SB
p53肿瘤抑制功能的丧失导致遗传不稳定性，其特征与染色体倍性和基因扩增的变化相关。在体内，我们发现，从4至6周龄的p53-nullizyzygov（p53（-/-））小鼠的各种器官的细胞显示非整倍体和频繁的基因扩增，以及细胞凋亡的证据。无论组织类型如何，许多p53（-/-）细胞含有多个中心体和异常形成的有丝分裂纺锤体。因此，体内染色体可能与异常有关。此外，我们观察到p53（-/-）小鼠中过表达c-Myc的细胞数量显着增加。与先前的研究表明c-Myc过表达与体外基因扩增相关一致，许多p53（-/-）细胞在同一细胞中表现出c-Myc过表达和扩增的c-Myc、二氢叶酸还原酶（DHFR）和氨甲酰基磷酸合成酶-天冬氨酸转氨甲酰基-二氢乳清酸酶（CAD）基因。此外，在从p53（-/-）小鼠分离的细胞中经常观察到凋亡。凋亡细胞中含有异常扩增的中心体，表现为非整倍体，c-Myc高水平表达，以及基因扩增。这些结果表明，大量的异常细胞在体内被p53非依赖性途径消除。
The loss of p53 tumor suppressor functions results in genetic instability, characteristically associated with changes in chromosome ploidy and gene amplification. In vivo, we find that cells from various organs of 4 to 6-week old p53-nullizygous (p53 (-/-)) mice display aneuploidy and frequent gene amplification as well as evidence for apoptosis. Regardless of tissue types, many p53 (-/-) cells contain multiple centrosomes and abnormally formed mitotic spindles. Thus, chromosome vivo may be associated with abnormal Moreover, we observed a significant increase in the number of cells overexpressing c-Myc in p53 (-/-) mice. Consistent with previous studies showing that c-Myc overexpression is associated with gene amplification in vitro, many of the p53 (-/-) cells exhibited, in the same cell, c-Myc overexpression and amplified c-myc, dihydrofolate reductase (DHFR), and carbamoyl-phosphate synthetase-aspartate transcarbamoyl-dihydroorotase (CAD) genes. Furthermore, apoptosis was frequently observed in cells isolated from p53 (-/-) mice. The apoptotic cells contained abnormally amplified centrosomes, displayed aneuploidy, high levels of c-Myc expression, as web as gene amplification. These results indicate that a high number of aberrant cells is eliminated by p53-independent pathways in vivo.