Titre
Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression.
Type
article
Institution
Externe
Périodique
Auteur(s)
Oricchio, E.
Auteure/Auteur
Sciamanna, I.
Auteure/Auteur
Beraldi, R.
Auteure/Auteur
Tolstonog, G.V.
Auteure/Auteur
Schumann, G.G.
Auteure/Auteur
Spadafora, C.
Auteure/Auteur
Liens vers les personnes
ISSN
0950-9232
Statut éditorial
Publié
Date de publication
2007-06-21
Volume
26
Numéro
29
Première page
4226
Dernière page/numéro d’article
4233
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Transformed cells express high levels of non-telomeric reverse-transcriptase (RT) activity of retrotransposon and endogenous retrovirus origin. We previously reported that RT inhibition, either pharmacological or through transient silencing of RT-encoding LINE-1 (L1) elements by RNA interference (RNAi), reduced proliferation, induced differentiation and reprogrammed gene expression in human tumorigenic cell lines. Moreover, the antiretroviral drug efavirenz antagonized tumor progression in animal models in vivo. To get insight into the role of retroelements in tumorigenesis, we have now produced two cell lines derived from A-375 melanoma, in which the expression of either L1 retrotransposon, or HERV-K endogenous retrovirus, was stably suppressed by RNAi. Compared to the parental A-375 cell line, cells with stably interfered L1 expression show a lower proliferation rate, a differentiated morphology and lower tumorigenicity when inoculated in nude mice. L1 silencing modulates expression of several genes and, unexpectedly, also downregulates HERV-K expression. In HERV-K interfered cells, instead, L1 expression was unaffected, and cell proliferation and differentiation remained unchanged compared to parental A-375 cells. In vivo, however, their tumorigenic potential was found to be reduced after inoculation in nude mice. These results suggest that L1 and HERV-K play specific and distinct roles in cell transformation and tumor progression.
Sujets
PID Serval
serval:BIB_D64A8F36DE19
PMID
Open Access
Oui
Date de création
2017-12-15T15:14:52.532Z
Date de création dans IRIS
2025-05-21T00:01:45Z