PMID- 17237820 OWN - NLM STAT- MEDLINE DCOM- 20070815 LR - 20091103 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 26 IP - 29 DP - 2007 Jun 21 TI - Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression. PG - 4226-33 AB - 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. FAU - Oricchio, E AU - Oricchio E AD - Istituto Superiore di Sanita, Servizio BGSA, Rome, Italy. FAU - Sciamanna, I AU - Sciamanna I FAU - Beraldi, R AU - Beraldi R FAU - Tolstonog, G V AU - Tolstonog GV FAU - Schumann, G G AU - Schumann GG FAU - Spadafora, C AU - Spadafora C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070122 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (RNA, Small Interfering) RN - 0 (Retroelements) SB - IM MH - Animals MH - *Cell Differentiation/genetics MH - Cell Line, Tumor MH - *Cell Proliferation MH - Cell Transformation, Neoplastic/genetics MH - Disease Progression MH - Endogenous Retroviruses/*genetics MH - Genetic Vectors MH - Humans MH - Long Interspersed Nucleotide Elements/genetics/*physiology MH - Melanoma, Experimental/genetics/*pathology/prevention & control/virology MH - Mice MH - Mice, Nude MH - Neoplasm Transplantation MH - RNA, Small Interfering/genetics MH - *Retroelements/genetics EDAT- 2007/01/24 09:00 MHDA- 2007/08/19 09:00 CRDT- 2007/01/24 09:00 PHST- 2007/01/24 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2007/01/24 09:00 [entrez] AID - 1210214 [pii] AID - 10.1038/sj.onc.1210214 [doi] PST - ppublish SO - Oncogene. 2007 Jun 21;26(29):4226-33. doi: 10.1038/sj.onc.1210214. Epub 2007 Jan 22.