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表皮生长因子(EGF)促进具有c-myc和junB原癌基因激活的分化滋养层细胞表型的发育。

EGF promotes development of a differentiated trophoblast phenotype having c-myc and junB proto-oncogene activation.

作者信息

Dakour J, Li H, Chen H, Morrish D W

机构信息

Department of Medicine, Heritage Medical Research Centre, University of Alberta, Edmonton, Canada.

出版信息

Placenta. 1999 Jan;20(1):119-26. doi: 10.1053/plac.1998.0336.

DOI:10.1053/plac.1998.0336
PMID:9950153
Abstract

Human placental cytotrophoblast cells differentiate by a process of fusion into a syncytium. This process is stimulated by EGF but also occurs spontaneously at a slower rate in cultured cytotrophoblast cells. To determine nuclear proto-oncogene changes mediating these events, c-myc, c-fos, c-jun and junB were measured in spontaneously differentiating cells and in cells exposed to EGF. c-myc showed a transient rise in expression at 4-8 h with augmented expression by EGF, occurring even in the absence of serum or attachment. c-myc and c-jun declined during culture, but c-fos and particularly junB showed increased expression by day 3 with marked responses to EGF stimulation. Syncytia induced to form by EGF exposure for 48 h demonstrated marked junB expression after rechallenge with 40 min EGF exposure, but negligible responses of c-fos and c-jun. c-myc showed increased expression after 6 h EGF exposure throughout the culture period and in syncytia. The results indicate EGF promotes a syncytial phenotype characterized by c-fos and junB expression during syncytial formation. EGF continues to elicit junB and c-myc responsiveness in more mature syncytium, indicative of continued EGF actions which may include acting as a survival factor, as an hCG secretagogue, and as an inducer of continued development of the syncytium.

摘要

人胎盘细胞滋养层细胞通过融合过程分化为合体滋养层。这个过程受表皮生长因子(EGF)刺激,但在培养的细胞滋养层细胞中也会以较慢的速率自发发生。为了确定介导这些事件的核原癌基因变化,对自发分化的细胞以及暴露于EGF的细胞中的c-myc、c-fos、c-jun和junB进行了检测。c-myc在4-8小时表达出现短暂上升,EGF可增强其表达,即使在无血清或细胞贴壁的情况下也会发生。在培养过程中,c-myc和c-jun表达下降,但c-fos尤其是junB在第3天表达增加,对EGF刺激有明显反应。经48小时EGF暴露诱导形成的合体滋养层在再次暴露于EGF 40分钟后显示出明显的junB表达,但c-fos和c-jun反应可忽略不计。在整个培养期以及合体滋养层中,c-myc在EGF暴露6小时后表达增加。结果表明,EGF在合体滋养层形成过程中促进了以c-fos和junB表达为特征的合体滋养层表型。EGF在更成熟的合体滋养层中继续引发junB和c-myc反应,这表明EGF持续发挥作用,可能包括作为生存因子、人绒毛膜促性腺激素(hCG)分泌刺激物以及合体滋养层持续发育的诱导剂。

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