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

// Chiara De Luca 1 , Fiorella Guadagni 2 , Paola Sinibaldi-Vallebona 3, 6 , Steno Sentinelli 4 , Michele Gallucci 4 , Andreas Hoffmann 5 , Gerald G. Schumann 5 , Corrado Spadafora 6 , Ilaria Sciamanna 1 1 Istituto Superiore di Sanita, SBGSA, Rome, Italy 2 Laboratory BioDAT SR Research, IRCCS San Raffaele Pisana, Rome, Italy 3 Department of Experimental Medicine and Surgery, University “Tor Vergata”, Rome, Italy 4 I.F.O. Regina Elena, UOC Pathological Anatomy/Urology, Rome, Italy 5 Department of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany 6 Institute 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.