Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Oricchio E,Sciamanna I,Beraldi R,Tolstonog GV,Schumann GG,Spadafora C

doi

10.1038/sj.onc.1210214

subject

Has Abstract

pub_date

2007-06-21 00:00:00

pages

4226-33

issue

29

eissn

0950-9232

issn

1476-5594

pii

1210214

journal_volume

26

pub_type

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