Nguyen Hao G, Ravid Katya
Department of Biochemistry and Medicine, Cancer Center, Boston University School of Medicine, Boston, Massachusetts, USA.
J Cell Physiol. 2006 Jul;208(1):12-22. doi: 10.1002/jcp.20565.
While polyploidy, a state of having fully duplicated sets of chromosomes per cell, has been described in normally developing bone marrow megakaryocytes or as an adaptive response in other cell types, aneuploidy is never detected in normal cells. Tetraploidy or aneuploidy can be induced by several signals and it is highly prevalent in different forms of cancers, suggesting a role for this cell cycle state in promoting cellular transformation. Investigations suggested that loss of heterozygosity of cancer-related genes in stem cells might contribute to genetic instability in progeny cells and to subsequent cancer development. Deregulated expression of chromosome passenger proteins, such as Aurora kinases or Survivin, is a hallmark of various cancers, and experimentally induced changes in these regulators can promote tetraploidy or aneuploidy and loss of heterozygosity. Our studies described an induction of tetraploidy/aneuploidy by a stable form of Aurora-B, leading to acquisition of transformation properties. It is intriguing to speculate that in some cancers, tetraploidy/aneuploidy induced by deregulated expression of a mitotic regulator represents a primary event that leads to unbalanced expression of a cluster of crucial genes and to cellular transformation.
虽然多倍体（即每个细胞具有完全复制的染色体组的状态）已在正常发育的骨髓巨核细胞中有所描述，或作为其他细胞类型的一种适应性反应，但非整倍体在正常细胞中从未被检测到。四倍体或非整倍体可由多种信号诱导，且在不同形式的癌症中高度普遍，这表明这种细胞周期状态在促进细胞转化中起作用。研究表明，干细胞中癌症相关基因杂合性的丧失可能导致子代细胞的遗传不稳定以及随后的癌症发展。染色体乘客蛋白（如极光激酶或生存素）的失调表达是各种癌症的一个标志，实验诱导这些调节因子的变化可促进四倍体或非整倍体以及杂合性的丧失。我们的研究描述了一种稳定形式的极光 - B诱导四倍体/非整倍体，导致获得转化特性。有趣的是推测，在某些癌症中，有丝分裂调节因子失调表达诱导的四倍体/非整倍体代表了一个原发性事件，导致一组关键基因的表达失衡并引发细胞转化。
