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

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 but not in differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promote differentiation in neoplastic cells, indicating that high endogenous RT activity promote cancer growth. Here we investigate the expression of L1-ORF2p in several human types ocancer.We have developed a highly specific monoclonal antibody (mAb chA1-L1) raised against the endonuclease domain of L1-ORF2p as a tool to study ORF2p expression and localization in human cancer cell lines and staged bioptic 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 cancer tissues shows ORF2p expression in pre-neoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively. Our results show that L1-ORF2p is overexpressed in tumor tissues and in pre-neoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early cancer diagnostic biomarker.