title: Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation.
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.
authors.affiliation: Istituto Superiore di Sanità, SBGSA, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Luca
authors.affiliation: Laboratory BioDAT SR Research, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.affiliation: Department of Experimental Medicine and Surgery, University "Tor Vergata", Rome, Italy.|Institute of Translational Pharmacology, CNR, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sinibaldi-Vallebona
authors.affiliation: I.F.O. Regina Elena, UOC Pathological Anatomy/Urology, Rome, Italy.
authors.forename: Steno
authors.initials: S
authors.lastname: Sentinelli
authors.affiliation: I.F.O. Regina Elena, UOC Pathological Anatomy/Urology, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Gallucci
authors.affiliation: Department of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Department of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Schumann
authors.affiliation: Institute of Translational Pharmacology, CNR, Rome, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Spadafora
authors.affiliation: Istituto Superiore di Sanità, SBGSA, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sciamanna
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004720:Endonucleases / Q000276:immunology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012194:RNA-Directed DNA Polymerase / Q000276:immunology / Q000378:metabolism*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C531246:ORF2 protein, human; D012194:RNA-Directed DNA Polymerase; D004720:Endonucleases; D003850:Deoxyribonuclease I; C538849:LINE-1 endonuclease, human
keywords: LINE-1/L1; ORF2; retrotransposon; reverse transcriptase; tumorigenesis