An unexpected result emerging from completion of the genome sequencing project is that a large portion of mammalian genomes is constituted by retrotransposons. A large body of published data supports the conclusion that retrotransposons are biologically active elements and indicates that retrotransposition is an ongoing process in mammalian genomes. Retroelements can act as insertional mutagens altering the coding integrity of genes and, recently, have been found to also affect the expression of cellular genes at the epigenetic level: in this light, they are a potential threat in that these events can trigger the onset of several pathologies including cancer. Retroelement genes, and particularly the gene coding for reverse transcriptase (RT), are typically expressed at high levels in transformed cells and tumors. In recent work, we have found that drug-mediated inhibition of the endogenous RT activity, or silencing of expression of active retrotransposons of the LINE-1 family by RNA interference, down-regulate cell growth and induce the activation of differentiating functions in several cancer cell lines. Moreover, the inhibition of endogenous RT activity in vivo antagonizes the growth of human tumors in animal models. In this review, we discuss newly emerging concepts on the role of retrotransposons and suggest that an abnormally high level of the RT activity that they encode may contribute to the loss of control in the proliferation and differentiation programs typical of transformed cells. In this light, RT-coding elements may be regarded as promising targets in the development of novel, differentiation-inducing approaches to cancer therapy. © 2005 Wiley-Liss, Inc.

SINIBALDI VALLEBONA, P., Lavia, P., Garaci, E., Spadafora, C. (2006). A role for endogenous reverse transcriptase in tumorigenesis and as a target in differentiating cancer therapy. GENES, CHROMOSOMES & CANCER, 45(1), 1-10 [10.1002/gcc.20266].

A role for endogenous reverse transcriptase in tumorigenesis and as a target in differentiating cancer therapy

SINIBALDI VALLEBONA, PAOLA;GARACI, ENRICO;
2006-01-01

Abstract

An unexpected result emerging from completion of the genome sequencing project is that a large portion of mammalian genomes is constituted by retrotransposons. A large body of published data supports the conclusion that retrotransposons are biologically active elements and indicates that retrotransposition is an ongoing process in mammalian genomes. Retroelements can act as insertional mutagens altering the coding integrity of genes and, recently, have been found to also affect the expression of cellular genes at the epigenetic level: in this light, they are a potential threat in that these events can trigger the onset of several pathologies including cancer. Retroelement genes, and particularly the gene coding for reverse transcriptase (RT), are typically expressed at high levels in transformed cells and tumors. In recent work, we have found that drug-mediated inhibition of the endogenous RT activity, or silencing of expression of active retrotransposons of the LINE-1 family by RNA interference, down-regulate cell growth and induce the activation of differentiating functions in several cancer cell lines. Moreover, the inhibition of endogenous RT activity in vivo antagonizes the growth of human tumors in animal models. In this review, we discuss newly emerging concepts on the role of retrotransposons and suggest that an abnormally high level of the RT activity that they encode may contribute to the loss of control in the proliferation and differentiation programs typical of transformed cells. In this light, RT-coding elements may be regarded as promising targets in the development of novel, differentiation-inducing approaches to cancer therapy. © 2005 Wiley-Liss, Inc.
Pubblicato
Rilevanza internazionale
Abstract
Sì, ma tipo non specificato
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
Con Impact Factor ISI
androgen receptor; angiogenesis inhibitor; antineoplastic agent; antiretrovirus agent; cyclin D1; efavirenz; matrix metalloproteinase inhibitor; nevirapine; prostate specific antigen; protein farnesyltransferase inhibitor; retinoic acid; retinoic acid receptor; RNA directed DNA polymerase; RNA directed DNA polymerase inhibitor; transcription factor; valproic acid; acquired immune deficiency syndrome; breast cancer; cancer; cancer research; cancer therapy; carcinogenesis; cell differentiation; cell proliferation; chromosome; DNA binding; embryo development; embryonal carcinoma; enzyme inhibition; epigenetics; gene; gene expression; gene insertion; gene silencing; genome analysis; herv k gene; heterochromatin; human; intron; melanoma; methylation; mutagenesis; nonhuman; priority journal; retroposon; review; RNA interference; Saccharomyces; teratocarcinoma; testis cancer; animal; cell transformation; drug effect; enzymology; gene therapy; genetics; neoplasm; pathology; physiology; tumor cell line; Animalia; Mammalia; Animals; Antineoplastic Agents; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Gene Silencing; Gene Therapy; Humans; Neoplasms; Retroelements; Reverse Transcriptase Inhibitors; RNA-Directed DNA Polymerase
SINIBALDI VALLEBONA, P., Lavia, P., Garaci, E., Spadafora, C. (2006). A role for endogenous reverse transcriptase in tumorigenesis and as a target in differentiating cancer therapy. GENES, CHROMOSOMES & CANCER, 45(1), 1-10 [10.1002/gcc.20266].
SINIBALDI VALLEBONA, P; Lavia, P; Garaci, E; Spadafora, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39408
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