期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 85, 期 1, 页码 23-38出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-006-0104-y
关键词
tumorigenesis; HERV; endometrial carcinoma; cell fusion; TGF-beta
Endometrial carcinomas (EnCa) predominantly represent a steroid hormone-driven tumor initiated from prestages. The human endogenous retrovirus HERV-W envelope gene Syncytin-1 was significantly increased at the mRNA and protein levels in EnCa and prestages compared to controls. Steroid hormone treatment of primary EnCa cells and cell lines induced Syncytin-1 due to a new HERV-W estrogen response element and resulted in increased proliferation. Activation of the cAMP-pathway also resulted in Syncytin-1 upregulation, but in contrast to proliferation, classic cell-cell fusions similar to placental syncytiotrophoblasts occurred. Cell-cell fusions were also histologically identified in endometrioid EnCa tumors in vivo. Clonogenic soft agar experiments showed that Syncytin-1 is also involved in anchorage-independent colony growth as well as in colony fusions depending on steroid hormones or cAMP-activation. The posttranscriptional silencing of Syncytin-1 gene expression and a concomitant functional block of induced cell proliferation and cell-cell fusion with siRNAs proved the essential role of Syncytin-1 in these cellular processes. TGF-beta 1 and TGF-beta 3 were identified as main regulative factors, due to the finding that steroid hormone inducible TGF-beta 1 and TGF-beta 3 inhibited cell-cell fusion, whereas antibody-mediated TGF-beta neutralization induced cell-cell fusions. These results showed that induced TGF-beta could override Syncytin-1-mediated cell-cell fusions. Interactions between Syncytin-1 and TGF-beta may contribute to the etiology of EnCa progression and also help to clarify the regulation of cell-cell fusions occurring in development and in other syncytial cell tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据