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Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

机译:体外极化Caco-2肠上皮细胞的全球转录程序与正常结肠癌和结肠癌中的基因表达程序之间的平行性

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摘要

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at .
机译:翻译后机制与上皮细胞极性的发展有关,但在此过程中对基因表达和转录调控的模式知之甚少。我们在培养的人Caco-2细胞的细胞-细胞粘附引发的极化过程中表征了基因表达的时间模式,该极化过程在体内形成类似于肠上皮细胞的结构和功能极性。细胞间接触形成后,基因表达模式发生了明显的转变。与正常人结肠和结肠肿瘤中基因表达模式的比较显示,增殖的非极化Caco-2细胞中的模式与人结肠癌体内的模式相似,包括参与细胞增殖的基因的表达。在极化的Caco-2细胞中,该模式切换为一种与在正常结肠组织中更相似的模式,表明Caco-2细胞极化的转录调控与体内肠细胞分化过程相似。出乎意料的是,极化Caco-2细胞中基因表达的时间程序涉及信号途径的改变(例如,Wnt,Hh,BMP,FGF),其模式类似于体内肠上皮细胞迁移和分化期间的模式,尽管缺乏形态原梯度和与基质细胞的相互作用,原位鉴定肠上皮细胞。完整的数据集可在访问。

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