EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth.
EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth.
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DOI：
10.1186/1476-4598-12-56
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发表时间：
2013-06-10
期刊：
影响因子：
37.3
通讯作者：
Untergasser G
中科院分区：
文献类型：
--
作者：
Martowicz A;Rainer J;Lelong J;Spizzo G;Gastl G;Untergasser G
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，并且其过表达被认为支持肿瘤进展和转移。然而，以前从未研究过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（HMEC）增殖、迁移和分化的影响。通过腺病毒系统转染HMEC以瞬时过表达EpCAM。此后，使用真实的时间测量系统研究细胞增殖和迁移的变化。在增殖和极化的HMEC培养物中通过转录组分析评估靶基因表达。鸡绒毛尿囊膜（CAM）异种移植模型用于研究对HMEC体内生长的影响。EpCAM在HMEC中的过表达没有显著改变增殖或生长停滞细胞的基因表达谱。扩增的HMEC主要显示糖基化EpCAM同种型，并通过上调p27 KIP 1和p53抑制细胞增殖和迁移。EpCAM过表达的HMEC表现出E-cadherin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，并在体外保持更长的增殖能力。EpCAM过表达的HMEC异种移植在鸡胚中表现出增生性生长，缺乏管腔形成和鸡白细胞浸润增加。EpCAM通过诱导对TGF-β1介导的生长停滞的抗性并支持具有较长体外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过表达导致体内增生性生长。因此，我们认为EpCAM作为一个促生存因子抵消终端分化过程中正常乳腺。
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). 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. 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. 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.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
168.9
作者：
Gastl, G;Spizzo, G;Mikuz, G
通讯作者：
Mikuz, G
影响因子：
4.3
作者：
Garbe, James C.;Holst, Charles R.;Stampfer, Martha R.
通讯作者：
Stampfer, Martha R.
EP-CAM：人类上皮抗原是一种同粒细胞粘附分子。
影响因子：
7.8
作者：
Litvinov, S V;Velders, M P;Bakker, H A;Fleuren, G J;Warnaar, S O
通讯作者：
Warnaar, S O
影响因子：
3.8
作者：
Martowicz A;Spizzo G;Gastl G;Untergasser G
通讯作者：
Untergasser G