title: Human OCTN2 (SLC22A5) is down-regulated in virus- and nonvirus-mediated cancer.
abstract: The expression of carnitine plasma membrane transporter OCTN2 was evaluated in virus and nonvirus-mediated cancer. Both OCTN2 mRNA and protein levels were reduced in keratinocytes retrotransduced with HPV16 E6 and E7 compared with the control. The OCTN2 expression was reduced also in keratinocytes retrotransduced with the sole HPV16 E6. A similar down-regulation of OCTN2 mRNA level was observed in a naturally HPV16-infected cancer cell line, CaSki, harbouring several copies of HPV16 whole genome. The mechanism of down-regulation is not related to p53 transcriptional activity because in SAOS (p53-null) cell line, the restoration of p53 expression did not rescue OCTN2 expression. The treatment of keratinocytes retrotransduced with HPV16 E6 and E7 with 5-aza-cytidine rescued the OCTN2 expression, indicating that the mechanism of down-regulation is linked to DNA methylation. Low levels of mRNA expression of OCTN2 were found also in several nonvirus-related epithelial cancer cell lines. The treatment of those cell 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 generally down-regulated in virus and nonvirus-mediated epithelial cancers, probably via methylation of its promoter region.
authors.affiliation: Department of Cell Biology, University of Calabria, Via P. Bucci 4c 87036 Arcavacata di Rende, Italy.
authors.forename: Mariafrancesca
authors.initials: M
authors.lastname: Scalise
authors.forename: Michele
authors.initials: M
authors.lastname: Galluccio
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.forename: Iris
authors.initials: I
authors.lastname: Cornet
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Cesare
authors.initials: C
authors.lastname: Indiveri
mesh_terms: D000818:Animals; D015536:Down-Regulation; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D000074058:Solute Carrier Family 22 Member 5; D014407:Tumor Cells, Cultured
chemical_list: D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5