De Luca Chiara, Guadagni Fiorella, Sinibaldi-Vallebona Paola, Sentinelli Steno, Gallucci Michele, Hoffmann Andreas, Schumann Gerald G, Spadafora Corrado, Sciamanna Ilaria
Istituto Superiore di Sanità, SBGSA, Rome, Italy.
Laboratory BioDAT SR Research, IRCCS San Raffaele Pisana, Rome, Italy.
Oncotarget. 2016 Jan 26;7(4):4048-61. doi: 10.18632/oncotarget.6767.
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.
LINE-1（L1）逆转座子是内源性逆转录酶（RT）活性的一个来源，该活性作为L1编码的开放阅读框2蛋白（L1-ORF2p）的一部分而表达。L1元件在多种癌症类型中高度表达，而在大多数分化的体细胞组织中沉默。我们之前发现，RT抑制会降低肿瘤细胞的增殖并促进其分化，这表明高内源性RT活性会促进癌症生长。在此，我们研究了L1-ORF2p在几种人类癌症类型中的表达。我们开发了一种高度特异性的单克隆抗体（单克隆抗体chA1-L1），以研究ORF2p在人类癌细胞和组织中的表达及定位。我们发现了新的证据，即转化细胞系和分期上皮癌组织（结肠、前列腺、肺和乳腺）中存在高水平的L1-ORF2p，而在未转化细胞中未检测到或仅检测到基础水平的ORF2p表达。对结肠和前列腺组织的深入分析显示，在肿瘤前阶段，即分别为移行黏膜和前列腺上皮内瘤变（PIN）中存在ORF2p表达。我们的结果表明，L1-ORF2p在肿瘤以及肿瘤前的结肠和前列腺组织中过表达；后一发现表明，ORF2p可被视为一种潜在的早期诊断生物标志物。
