LINE-1 retrotransposition events affect endothelial proliferation and migration.
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.
Institute of Anatomy, University Hospital Essen, Essen, Germany. ferya.banaz-yasar@uk-essen.de
Ferya
F
Banaz-Yaşar
Gyde
G
Steffen
Jessica
J
Hauschild
Birthe M
BM
Bongartz
Gerald G
GG
Schumann
Süleyman
S
Ergün
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004720:Endonucleases / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D020084:Long Interspersed Nucleotide Elements / Q000502:physiology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D011471:Prostatic Neoplasms; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D042787:Receptor, TIE-2 / Q000096:biosynthesis; D013552:Swine; D013736:Testicular Neoplasms; D001749:Urinary Bladder Neoplasms; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D019394:Ki-67 Antigen; C531246:ORF2 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D012194:RNA-Directed DNA Polymerase; D004720:Endonucleases