Oncotarget

Research Papers:

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 and Ilaria Sciamanna _

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Oncotarget. 2016; 7:4048-4061. https://doi.org/10.18632/oncotarget.6767

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Abstract

Chiara De Luca1, Fiorella Guadagni2, Paola Sinibaldi-Vallebona3,6, Steno Sentinelli4, Michele Gallucci4, Andreas Hoffmann5, Gerald G. Schumann5, Corrado Spadafora6, Ilaria Sciamanna1

1Istituto Superiore di Sanità, SBGSA, Rome, Italy

2Laboratory BioDAT SR Research, IRCCS San Raffaele Pisana, Rome, Italy

3Department of Experimental Medicine and Surgery, University “Tor Vergata”, Rome, Italy

4I.F.O. Regina Elena, UOC Pathological Anatomy/Urology, Rome, Italy

5Department of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany

6Institute of Translational Pharmacology, CNR, Rome, Italy

Correspondence to:

Ilaria Sciamanna, email: ilaria.sciamanna@iss.it

Corrado Spadafora, email: cspadaf@tin.it

Keywords: retrotransposon, LINE-1/L1, ORF2, reverse transcriptase, tumorigenesis

Received: June 17, 2015     Accepted: November 30, 2015     Published: December 26, 2015

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.


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