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首页> 外文期刊>Molecular Cancer >EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth
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EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth

机译：EpCAM过表达可延长人乳腺上皮细胞的增殖能力并支持增生性生长

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Introduction The Epithelial Cell Adhesion Molecule ( EpCAM ) has been shown to be strongly expressed in human breast cancer and cancer stem cells and its overexpression has been supposed to support tumor progression and metastasis. However, effects of EpCAM overexpression on normal breast epithelial cells have never been studied before. Therefore, we analyzed effects of transient adenoviral overexpression of EpCAM on proliferation, migration and differentiation of primary human mammary epithelial cells (HMECs). Methods HMECs were transfected by an adenoviral system for transient overexpression of EpCAM . Thereafter, changes in cell proliferation and migration were studied using a real time measurement system. Target gene expression was evaluated by transcriptome analysis in proliferating and polarized HMEC cultures. A Chicken Chorioallantoic Membrane (CAM) xenograft model was used to study effects on in vivo growth of HMECs. Results EpCAM overexpression in HMECs did not significantly alter gene expression profile of proliferating or growth arrested cells. Proliferating HMECs displayed predominantly glycosylated EpCAM isoforms and were inhibited in cell proliferation and migration by upregulation of p27KIP1 and p53. HMECs with overexpression of EpCAM showed a down regulation of E-cadherin. Moreover, cells were more resistant to TGF-β1 induced growth arrest and maintained longer capacities to proliferate in vitro . EpCAM overexpressing HMECs xenografts in chicken embryos showed hyperplastic growth, lack of lumen formation and increased infiltrates of the chicken leukocytes. Conclusions EpCAM revealed oncogenic features in normal human breast cells by inducing resistance to TGF-β1 -mediated growth arrest and supporting a cell phenotype with longer proliferative capacities in vitro . EpCAM overexpression resulted in hyperplastic growth in vivo . Thus, we suggest that EpCAM acts as a prosurvival factor counteracting terminal differentiation processes in normal mammary glands.
机译：引言上皮细胞粘附分子（EpCAM）已显示在人乳腺癌和癌症干细胞中强烈表达，其过表达被认为可支持肿瘤的进展和转移。然而，从未研究过EpCAM过表达对正常乳腺上皮细胞的影响。因此，我们分析了瞬时腺病毒过表达EpCAM对原代人乳腺上皮细胞（HMECs）增殖，迁移和分化的影响。方法用腺病毒系统转染HMECs以瞬时过量表达EpCAM。此后，使用实时测量系统研究了细胞增殖和迁移的变化。通过转录组分析在增殖和极化HMEC培养物中评估靶基因的表达。鸡绒囊尿囊膜（CAM）异种移植模型用于研究对HMECs体内生长的影响。结果HMEC中EpCAM的过表达不会显着改变增殖或生长停止的细胞的基因表达谱。增殖的HMECs主要表现出糖基化的EpCAM亚型，并且通过上调p27 =“ KIP1 和p53而受到抑制。过度表达EpCAM的HMEC显示E-钙粘蛋白的下调。此外，细胞对TGF-β1诱导的生长停滞具有更强的抵抗力，并保持更长的体外增殖能力。鸡胚中EpCAM过表达的HMECs异种移植物显示增生性生长，管腔形成不足和鸡白细胞浸润增加。结论EpCAM通过诱导对TGF-β1介导的生长停滞的抗性并支持体外具有更长增殖能力的细胞表型，揭示了正常人乳腺细胞的致癌特征。 EpCAM的过表达导致体内增生生长。因此，我们建议EpCAM作为抵消正常乳腺终末分化过程的生存因子。

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