The expression of carnitine plasma membrane transporter OCTN2 was evaluated invirus and nonvirus-mediated cancer. Both OCTN2 mRNA and protein levels werereduced in keratinocytes retrotransduced with HPV16 E6 and E7 compared with thecontrol. The OCTN2 expression was reduced also in keratinocytes retrotransducedwith the sole HPV16 E6. A similar down-regulation of OCTN2 mRNA level wasobserved in a naturally HPV16-infected cancer cell line, CaSki, harbouringseveral copies of HPV16 whole genome. The mechanism of down-regulation is notrelated to p53 transcriptional activity because in SAOS (p53-null) cell line, therestoration of p53 expression did not rescue OCTN2 expression. The treatment ofkeratinocytes retrotransduced with HPV16 E6 and E7 with 5-aza-cytidine rescuedthe OCTN2 expression, indicating that the mechanism of down-regulation is linked to DNA methylation. Low levels of mRNA expression of OCTN2 were found also inseveral nonvirus-related epithelial cancer cell lines. The treatment of thosecell lines with 5-aza-cytidine again rescued the expression of OCTN2 as well.These data demonstrate for the first time that the OCTN2 transporter is generallydown-regulated in virus and nonvirus-mediated epithelial cancers, probably viamethylation of its promoter region

Human OCTN2 (SLC22A5) is down-regulated in virus- and nonvirus-mediated cancer

Scalise M;GALLUCCIO, Michele;INDIVERI, Cesare
2012

Abstract

The expression of carnitine plasma membrane transporter OCTN2 was evaluated invirus and nonvirus-mediated cancer. Both OCTN2 mRNA and protein levels werereduced in keratinocytes retrotransduced with HPV16 E6 and E7 compared with thecontrol. The OCTN2 expression was reduced also in keratinocytes retrotransducedwith the sole HPV16 E6. A similar down-regulation of OCTN2 mRNA level wasobserved in a naturally HPV16-infected cancer cell line, CaSki, harbouringseveral copies of HPV16 whole genome. The mechanism of down-regulation is notrelated to p53 transcriptional activity because in SAOS (p53-null) cell line, therestoration of p53 expression did not rescue OCTN2 expression. The treatment ofkeratinocytes retrotransduced with HPV16 E6 and E7 with 5-aza-cytidine rescuedthe OCTN2 expression, indicating that the mechanism of down-regulation is linked to DNA methylation. Low levels of mRNA expression of OCTN2 were found also inseveral nonvirus-related epithelial cancer cell lines. The treatment of thosecell lines with 5-aza-cytidine again rescued the expression of OCTN2 as well.These data demonstrate for the first time that the OCTN2 transporter is generallydown-regulated in virus and nonvirus-mediated epithelial cancers, probably viamethylation of its promoter region
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/134004
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