Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation
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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
Ilaria Sciamanna, email: [email protected]
Corrado Spadafora, email: [email protected]
Keywords: retrotransposon, LINE-1/L1, ORF2, reverse transcriptase, tumorigenesis
Received: June 17, 2015 Accepted: November 30, 2015 Published: December 26, 2015
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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