Nitric Oxide Control of MYCN Expression and Multi Drug Resistance Genes in Tumours of Neural Origin

Antonio      Porro; Christophe      Chrochemore; Francesco      Cambuli; Nunzio      Iraci; Antonio      Contestabile; Giovanni      Perini

Abstract

Nitric oxide (NO) exerts its function in several cell and organ compartments. Recently, several lines of evidence have been accrued showing that NO can play a critical role in oncogenesis. Here we summarize some of these findings and highlight the role of NO as a possible target for antineoplastic drugs. Specifically, NO appears to affect some aspects of neuronal tumour progression, particularly the chemoresistance phenotype, through inhibition of MYC activity and expression of a large set of ATP binding cassette transporters. Here we provide lines of evidence supporting the view that MYCN can alter expression of several members of the ABC transporter family thus influencing the chemoresistance phenotype of neuroblastoma cells. Furthermore, we show that increased intracellular NO concentration either through addition of NO donors to culture medium or through forced expression of nNOS in neuroblastoma cells leads to decreased expression of MYCN and ABC drug transporter genes. Overall, data reviewed here and novel results presented, unveil a NO-MYCN-ABC transporters axis with important implication on development and control of the chemoresistance phenotype in neuronal tumours.

Keywords: MYCN, nitric oxide, ABC transporter genes, neuronal tumours, neuroblastoma

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