细胞动力学失败产生四体,促进p53-null细胞中的瘤发生
Takeshi Fujiwara1, Madhavi Bandi, Masayuki Nitta
1Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|October 14, 2005
概括
细胞分裂失败会产生四形细胞,促进遗传不稳定性和癌症. 四体细胞,但不是双体细胞,发展成恶性乳腺瘤,表现为四体性.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 瘤发生假设涉及细胞分裂失败导致遗传不稳定的四形细胞.
- 四形细胞可能促进形瘤恶性瘤的发展.
研究的目的:
- 测试假设细胞分裂失败和随后的四化促进瘤发生的假设.
- 为了研究四化在染色体不稳定性和恶性转变中的作用.
主要方法:
- 在p53-null小鼠乳腺上皮细胞 (MMEC) 中暂时阻断细胞动能,以分离二倍体和四倍体培养物.
- 在两种细胞类型中评估染色体不稳定性 (错误分离,重新排列).
- 评估在暴露于致癌物质后的体外转化和在裸体小鼠皮下移植后的体内瘤性.
主要成果:
- 与二倍体细胞相比,四倍体MMECs表现出增加的全染色体错误分离和染色体重排.
- 只有四形细胞在暴露于致癌物质后在体外进行了转化.
- 移植的四倍体细胞,但不是双倍体细胞,形成了恶性乳腺上皮癌,其特征是转位和矩阵金属蛋白酶 (MMP) 基因放大.
结论:
- 四化显著增加了p53-null MMECs中的染色体变异的频率.
- 四体是促进恶性乳腺上皮癌发展的关键因素.
- 这些发现支持了长期以来的假设,将细胞分裂失败,四体和瘤产生联系起来.
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