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.

Of all human endogenous retroviruses known today, HERV-K is the only one that has been shown to produce viral particles. While the first of the approximately 30 HERV-K sequences integrated into the human genome more than 40 million years ago, evidence is accumulating that HERV-K was active more recently, provirus HERV-K113 being the youngest sequence found. However, it is unclear which HERV-K sequences code for the viral particles that are produced by human germ-cell tumours or melanomas. Here, we show that the provirus HERV-K113, cloned into a baculovirus expression vector, is capable of producing intact particles of retroviral morphology, exhibiting the typical structure of those particles that were characterized in cell lines derived from human germ-cell tumours. Thus, the HERV-K113 sequence is a candidate for particle production in vivo and for an active human endogenous retrovirus of today.