Richardson B D, Cheng Y H, Langland R A, Handwerger S
Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA. brian.richardson.chmcc.org
Life Sci. 2001 Sep 21;69(18):2157-65. doi: 10.1016/s0024-3205(01)01299-1.
Previous studies from our laboratory demonstrated that AP-2alpha induces the expression of the hPL and hCG genes in cultured trophoblast cells. In the current study, we have shown by transient transfection studies that AP-2gamma, which is the product of a separate gene from AP-2alpha, also stimulates hPL and hCGbeta promoter activities. However, AP-2gamma mRNA levels during in vitro differentiation of human cytotrophoblast cells were strikingly different than those of AP-2alpha mRNA levels, with AP-2alpha increasing and AP-2gamma markedly decreasing during the differentiation process. The amount of AP-2gamma protein binding to AP-2 elements on the hPL promoter, as determined by supershift assays, also markedly decreased during the differentiation process. These findings strongly suggest that AP-2gamma action in cytotrophoblast cells is repressed by a co-factor(s) that inhibits AP-2gamma action or is prevented by the absence of a co-factor(s) that is essential for AP-2gamma action.
我们实验室之前的研究表明,AP-2α可诱导培养的滋养层细胞中hPL和hCG基因的表达。在当前研究中,我们通过瞬时转染研究表明,AP-2γ(它是与AP-2α不同基因的产物)也能刺激hPL和hCGβ启动子活性。然而,人细胞滋养层细胞体外分化过程中AP-2γ mRNA水平与AP-2α mRNA水平显著不同,在分化过程中AP-2α增加而AP-2γ明显下降。通过超迁移分析确定,与hPL启动子上AP-2元件结合的AP-2γ蛋白量在分化过程中也显著减少。这些发现强烈表明,细胞滋养层细胞中AP-2γ的作用受到抑制AP-2γ作用的一种或多种辅因子的抑制,或者因缺乏对AP-2γ作用至关重要的一种或多种辅因子而受到阻碍。