Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are directly linked to cell transformation. To address this possibility, we have employed two different approaches to inhibit RT activity in melanoma and prostate carcinoma cell fines: pharmacological inhibition by two characterized RT inhibitors, nevirapine and efavirenz, and downregulation of expression of RT-encoding LINE-1 elements by RNA interference (RNAi). Both treatments reduced proliferation, induced morphological differentiation and reprogrammed gene expression. These features are reversible upon discontinuation of the anti-RT treatment, suggesting that RT contributes to an epigenetic level of control. Most importantly, inhibition of RT activity in vivo antagonized tumor growth in animal experiments. Moreover, pretreatment with RT inhibitors attenuated the tumorigenic phenotype of prostate carcinoma cells inoculated in nude mice. Based on these data, the endogenous RT can be regarded as an epigenetic regulator of cell differentiation and proliferation and may represent a novel target in cancer therapy.

Sciamanna, I., Landriscina, M., Pittoggi, C., Quirino, M., Mearelli, C., Beraldi, R., et al. (2005). Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. ONCOGENE, 24(24), 3923-3931 [10.1038/sj.onc.1208562].

Inhibition of endogenous reverse transcriptase antagonizes human tumor growth

SINIBALDI VALLEBONA, PAOLA;GARACI, ENRICO;
2005-01-01

Abstract

Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are directly linked to cell transformation. To address this possibility, we have employed two different approaches to inhibit RT activity in melanoma and prostate carcinoma cell fines: pharmacological inhibition by two characterized RT inhibitors, nevirapine and efavirenz, and downregulation of expression of RT-encoding LINE-1 elements by RNA interference (RNAi). Both treatments reduced proliferation, induced morphological differentiation and reprogrammed gene expression. These features are reversible upon discontinuation of the anti-RT treatment, suggesting that RT contributes to an epigenetic level of control. Most importantly, inhibition of RT activity in vivo antagonized tumor growth in animal experiments. Moreover, pretreatment with RT inhibitors attenuated the tumorigenic phenotype of prostate carcinoma cells inoculated in nude mice. Based on these data, the endogenous RT can be regarded as an epigenetic regulator of cell differentiation and proliferation and may represent a novel target in cancer therapy.
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
RNA directed DNA polymerase; RNA directed DNA polymerase inhibitor; broxuridine; enzyme inhibitor; small interfering RNA; article; cancer therapy; cell differentiation; cell growth; controlled study; embryo cell; enzyme inhibition; gene targeting; genetic epigenesis; human; human cell; human tissue; in vivo study; melanoma; priority journal; prostate carcinoma; regulator gene; retroposon; tumor growth; cell cycle; cell division; confocal microscopy; drug effect; metabolism; pathology; reverse transcription polymerase chain reaction; tumor cell line; Animalia; Mus musculus; Bromodeoxyuridine; Cell Cycle; Cell Division; Cell Line, Tumor; Enzyme Inhibitors; Humans; Melanoma; Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; RNA-Directed DNA Polymerase
Sciamanna, I., Landriscina, M., Pittoggi, C., Quirino, M., Mearelli, C., Beraldi, R., et al. (2005). Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. ONCOGENE, 24(24), 3923-3931 [10.1038/sj.onc.1208562].
Sciamanna, I; Landriscina, M; Pittoggi, C; Quirino, M; Mearelli, C; Beraldi, R; Mattei, E; Serafino, A; Cassano, A; SINIBALDI VALLEBONA, P; Garaci, E; Barone, C; Spadafora, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39413
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