Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation

Chiara De Luca, Fiorella Guadagni, Paola Sinibaldi-Vallebona, Steno Sentinelli, Michele Gallucci, Andreas Hoffmann, Gerald G. Schumann, Corrado Spadafora, Ilaria Sciamanna

Research output: Contribution to journalArticle

Abstract

LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types, while being silenced in most differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promotes differentiation in neoplastic cells, indicating that high endogenous RT activity promotes cancer growth. Here we investigate the expression of L1-ORF2p in several human types of cancer. We have developed a highly specific monoclonal antibody (mAb chA1-L1) to study ORF2p expression and localization in human cancer cells and tissues. We uncover new evidence for high levels of L1-ORF2p in transformed cell lines and staged epithelial cancer tissues (colon, prostate, lung and breast) while no or only basal ORF2p expression was detected in non-transformed cells. An in-depth analysis of colon and prostate tissues shows ORF2p expression in preneoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively. Our results show that L1-ORF2p is overexpressed in tumor and in preneoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early diagnostic biomarker.

Original languageEnglish
Pages (from-to)4048-4061
Number of pages14
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 2016

Keywords

  • LINE-1/L1
  • ORF2
  • Retrotransposon
  • Reverse transcriptase
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology

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    De Luca, C., Guadagni, F., Sinibaldi-Vallebona, P., Sentinelli, S., Gallucci, M., Hoffmann, A., Schumann, G. G., Spadafora, C., & Sciamanna, I. (2016). Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation. Oncotarget, 7(4), 4048-4061. https://doi.org/10.18632/oncotarget.6767