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Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer
Department of Experimental Medicine and Biochemical Sciences, University ‘Tor Vergata’, Rome, Italy
Italian National Institute of Health (ISS), Rome, Italy
* Author to whom correspondence should be addressed.
Received: 11 January 2011; in revised form: 21 February 2011 / Accepted: 22 February 2011 / Published: 7 March 2011
Abstract: LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti-cancer therapy.
Keywords: tumorigenesis; endogenous reverse transcriptase; reverse transcriptase inhibitors; early embryonic development
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Sinibaldi-Vallebona, P.; Matteucci, C.; Spadafora, C. Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer. Cancers 2011, 3, 1141-1157.
Sinibaldi-Vallebona P, Matteucci C, Spadafora C. Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer. Cancers. 2011; 3(1):1141-1157.
Sinibaldi-Vallebona, Paola; Matteucci, Claudia; Spadafora, Corrado. 2011. "Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer." Cancers 3, no. 1: 1141-1157.