TY - JOUR
T1 - Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation
AU - De Luca, Chiara
AU - Guadagni, Fiorella
AU - Sinibaldi-Vallebona, Paola
AU - Sentinelli, Steno
AU - Gallucci, Michele
AU - Hoffmann, Andreas
AU - Schumann, Gerald G.
AU - Spadafora, Corrado
AU - Sciamanna, Ilaria
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - LINE-1/L1
KW - ORF2
KW - Retrotransposon
KW - Reverse transcriptase
KW - Tumorigenesis
UR - http://www.scopus.com/inward/record.url?scp=84957990142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957990142&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6767
DO - 10.18632/oncotarget.6767
M3 - Article
AN - SCOPUS:84957990142
VL - 7
SP - 4048
EP - 4061
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 4
ER -