Location of cell cycle regulators cyclin B1, cyclin A, PCNA, Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas
Location of cell cycle regulators cyclin B1, cyclin A, PCNA, Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas
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DOI：
10.1007/s00418-006-0160-y
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发表时间：
2006-06-01
影响因子：
2.3
通讯作者：
Demir, R
中科院分区：
文献类型：
--
作者：
Korgun, ET;Celik-Ozenci, C;Demir, R
虽然胎盘发育和着床依赖于滋养层细胞增殖、分化和侵袭的协调，但对控制这些事件的细胞周期调节因子知之甚少。细胞周期进程和抑制因子的协同表达将决定细胞滋养层细胞是增殖还是经历细胞周期停滞或细胞周期退出，从而允许随后的分化，这一假设得到了检验。细胞周期促进因子细胞周期蛋白A、细胞周期蛋白B1、增殖细胞核抗原、细胞周期抑制因子Ki67和细胞周期抑制因子p21、p27、p57在妊娠早期(6周和9-12周)的组织切片中均有免疫组织化学定位。细胞角蛋白7双重染色可以明确识别蜕膜中的绒毛外细胞滋养细胞(EVT)。绒毛细胞滋养层细胞免疫标记Ki67和细胞周期蛋白A，但仅少数细胞周期蛋白B1染色。合体滋养层细胞对任何细胞周期推进因子均无免疫反应。P21主要表达于绒毛细胞滋养层细胞，p27和p57主要表达于绒毛细胞滋养层细胞。增殖细胞核抗原、Ki67、细胞周期蛋白A和细胞周期蛋白B1在锚定绒毛近端、远端和侵犯上蜕膜段的早孕绒毛中均有表达。所有EVT均强表达p27和p57，但不表达p21。这些数据清楚地提示了p21、p27和p57在胎盘发育中的不同功能，其中p21和p57分别在合体滋养层细胞和EVT分化中起着不同的作用。P27似乎参与了这两个过程。这一结果也可能挑战妊娠早期细胞滋养层细胞柱近端和远端不同有丝分裂活性的概念，但显然还需要更多的功能研究。深入蜕膜的EVT细胞中p27和p57的存在可能是这些细胞失去有丝分裂潜能的原因。
Although placental development and implantation depend on the coordination of trophoblast proliferation, differentiation and invasion, little is known about the cell cycle regulators that govern the control of these events. The hypothesis that the coordinated expression of cell cycle progression and inhibition factors will determine whether cytotrophoblasts proliferate or undergo cell cycle arrest or cell cycle exit allowing subsequent differentiation was tested. The cell cycle promotors cyclin A, cyclin B1, PCNA, Ki67 and the cell cycle inhibitors p21, p27 and p57 were immunolocalized in tissue sections of first trimester pregnancies (weeks 6 and 9-12). Double staining with cytokeratin 7 allowed unambiguous identification of extravillous cytotrophoblast (EVT) in the decidua. Villous cytotrophoblasts were immunolabelled for Ki67 and cyclin A but only few were stained with anti-cyclin B1. The syncytiotrophoblast was devoid of immunoreactivity for any of the cell cycle progression factors. It expressed especially p21, whereas p27 and p57 were predominantly found in villous cytotrophoblasts. PCNA, Ki67, cyclin A and cyclin B1 were immunolocalized in proximal and distal EVTs of anchoring villi and in EVT which had invaded the upper decidual segments. All EVTs strongly expressed p27 and p57, but not p21. These data clearly suggest different functions for p21, p27 and p57 in placental development with distinct roles for p21 and p57 in syncytiotrophoblast and EVT differentiation, respectively. p27 appears to be involved in both the processes. The results may also challenge the concept of differential mitotic activity in the proximal and distal parts of the first trimester cytotrophoblast cell column, but more functional studies are clearly needed. The presence of p27 and p57 in EVT cells, which invade the deciduas deeply, may account for the loss of mitogenic potential of these cells.