滋养层
巨细胞
细胞生物学
生物
细胞分化
下调和上调
E2F型
细胞周期
胎盘
细胞凋亡
基因
遗传学
胎儿
怀孕
作者
Veronica Soloveva,Daniel I. H. Linzer
出处
期刊:Placenta
[Elsevier]
日期:2004-01-01
卷期号:25 (1): 29-36
被引量:39
标识
DOI:10.1016/s0143-4004(03)00215-7
摘要
Trophoblast giant cells in the rodent placenta form the outermost layer of the extraembryonic compartment, establish direct contact with maternal cells, and produce a number of pregnancy-specific cytokine hormones. Giant cells differentiate from proliferative trophoblasts as they exit the cell cycle and enter a genome-amplifying endocycle, a process we show involves decreased expression of the G1 checkpoint proteins p53 and Rb. Although p53 mRNA levels are unchanged in proliferative compared to differentiated trophoblasts, p53 protein levels are markedly reduced in giant cells. Forced expression of wild type p53 in trophoblasts inhibits differentiation, and expression of a dominant negative p53 peptide stimulates differentiation. Consistent with the loss of p53 protein, differentiated trophoblasts become resistant to apoptosis-inducing agents. Decreased expression of Rb is also detected during differentiation, and overexpression of Rb in trophoblasts inhibits giant cell differentiation. Although an increase in E2F activity would be expected with the loss of Rb, what is observed is an overall decrease in E2F DNA-binding complexes, a shift to new complexes, and a decrease in E2F-dependent gene expression in differentiating trophoblasts. Overall, these results indicate that the combination of a decrease in p53 and Rb represents a functionally important part of the transition of trophoblasts from a proliferative cell cycle to an endocycle in the giant cell differentiation programme.
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