LINE-1 retrotransposition events affect endothelial proliferation and migration |
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Authors: | Ferya Banaz-Yaşar Gyde Steffen Jessica Hauschild Birthe M. Bongartz Gerald G. Schumann Süleyman Ergün |
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Affiliation: | (1) Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany;(2) Institute of Anatomy I, University Hospital Hamburg-Eppendorf, Hamburg, Germany;(3) Paul-Ehrlich-Institute, Langen, Germany |
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Abstract: | Long interspersed nuclear element-1 (LINE-1, L1) is a retrotransposon which affects the human genome by a variety of mechanisms. While LINE-1 expression is suppressed in the most somatic human cells, LINE-1 elements are activated in human cancer. Recently, high accumulation of LINE-1-encoded ORF1p and ORF2p in endothelial cells of mature human blood vessels was described. Here, we demonstrate that LINE-1 de novo retrotransposition events lead to a reduction of endothelial cell proliferation and migration in a porcine aortic endothelial (PAE) cell model. Cell cycle studies show a G0/G1 arrest in PAE cells harboring LINE-1 de novo retrotransposition events. Remarkably, in in situ analysis LINE-1-encoded ORF2p was not detectable in tumor blood vessels of different human organs while vascular endothelial cells of corresponding normal organs strongly expressed LINE-1 ORF2p. Quantitative RT-PCR analysis revealed that LINE-1 de novo retrotransposition influences selectively the expression of some angiogenic factors such as VEGF and Tie-2. Thus, our data suggest that LINE-1 de novo retrotransposition events might suppress angiogenesis and tumor vascularisation by reducing the angiogenic capacity of vascular endothelial cells. |
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