Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral Syncytin-1 and regulated by TGF-beta

J Mol Med (Berl). 2007 Jan;85(1):23-38. doi: 10.1007/s00109-006-0104-y. Epub 2006 Oct 26.


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-beta1 and TGF-beta3 were identified as main regulative factors, due to the finding that steroid hormone inducible TGF-beta1 and TGF-beta3 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Blotting, Northern
  • Blotting, Southern
  • Blotting, Western
  • Cell Fusion
  • Cell Proliferation*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Female
  • Gene Expression Profiling
  • Gene Products, env / antagonists & inhibitors
  • Gene Products, env / genetics
  • Gene Products, env / metabolism*
  • Gene Silencing / physiology
  • Humans
  • Immunoblotting
  • Middle Aged
  • Pregnancy Proteins / antagonists & inhibitors
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured / drug effects


  • Gene Products, env
  • Pregnancy Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • syncytin