一种将额外的中枢细胞与染色体不稳定性联系起来的机制
Neil J Ganem1, Susana A Godinho, David Pellman
1Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|June 10, 2009
概括
额外的中心体在癌症中引起染色体不稳定性 (CIN),因为它在双极细胞分裂过程中促进染色体错误分离,而不是多极细胞分裂. 这阐明了一个关键的机制,将额外的中心细胞与瘤发展联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 遗传学 是一个遗传学.
背景情况:
- 染色体不稳定性 (CIN) 是许多瘤的共同特征.
- CIN通常与额外的中心体存在相关.
- 额外中心体和CIN之间的机制联系仍然不清楚.
研究的目的:
- 调查额外中心体和染色体不稳定性 (CIN) 之间的机械联系.
- 通过多极分裂或其他机制来确定额外的中枢细胞是否直接导致CIN.
- 阐明癌细胞中额外的中心体引起的特定的线粒性缺陷.
主要方法:
- 长期活细胞成像,对具有不同中心体数量的细胞进行成像.
- 细胞系的产生仅仅在中心细胞数量上有所不同.
- 对细胞分裂模式的分析,包括多极和双极分裂,以及染色体分离的准确性.
主要成果:
- 拥有额外中心体的细胞很少经历多极分裂,它们的后代通常是不可行的.
- 具有额外中心体的CIN细胞在双极分裂期间主要表现出增加的染色体滞后.
- 额外的中枢细胞单独就足以在双极分裂期间通过短暂的多极中间体引起染色体分离错误.
结论:
- 额外的中心细胞驱动染色体不稳定性 (CIN),主要是通过促进染色体错误分离在双极分裂,而不是多极分裂.
- 一个短暂的多极中间体允许 merotelic 附着错误,导致 CIN.
- 这种机制提供了额外中心体和CIN之间的直接联系,可能解释了许多人类癌症中的CIN.
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