title: Differential Expression of Ion Channels and Transporters During Hepatocellular Carcinoma Development.
abstract: BACKGROUND
  Ion channels and transporters are potential markers and therapeutic targets for several cancers. However, their expression during hepatocellular carcinoma (HCC) development remains unclear.
  
  
  OBJECTIVE
  To investigate the mRNA expression of Na(+), K(+) and Ca(2+) channels and ABC transporters during rat HCC development, as well as Abcc3 protein in human liver biopsies.
  
  
  METHODS
  Wistar rats were treated with diethylnitrosamine (DEN) and developed both cirrhosis (12 weeks of treatment) and either pre-neoplastic lesions (16 weeks of treatment) or multinodular HCC (16 weeks of treatment plus 2 weeks DEN-free). The mRNA expression of 12 ion channels and two ABC transporters was studied using real-time RT-PCR. Tumor-containing or tumor-free liver sections were isolated by laser-capture microdissection. Abcc3 protein expression was studied by immunohistochemistry in healthy, cirrhotic and HCC human biopsies.
  
  
  RESULTS
  We observed expression changes in seven genes. Kcna3, Kcnn4, Kcnrg and Kcnj11 potassium channel mRNA expression reached peak values at the end of DEN treatment, while Scn2a1 sodium channel, Trpc6 calcium channel and Abcc3 transporter mRNA expression reached their highest levels in the presence of HCC (18 weeks). Whereas Kcnn4 and Scn2a1 channel expression was similar in non-tumor and tumor tissue, the Abcc3 transporter and Kcna3 potassium channels were preferentially overexpressed in the tumor sections. We observed differential Abcc3 protein subcellular localization and expression in human samples.
  
  
  CONCLUSIONS
  The ion channel/transporter expression profile observed suggests that these genes are potential early markers or therapeutic targets of HCC. The differential localization of Abcc3 may be useful in the diagnosis of cirrhosis and HCC.
authors.affiliation: Department of Pharmacology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, C.P. 07360, Mexico City, Mexico, vzuniga@cinvestav.mx.
authors.forename: Violeta
authors.initials: V
authors.lastname: Zúñiga-García
authors.forename: María de Guadalupe
authors.initials: Mde G
authors.lastname: Chávez-López
authors.forename: Valeria
authors.initials: V
authors.lastname: Quintanar-Jurado
authors.forename: Nayeli Belem
authors.initials: NB
authors.lastname: Gabiño-López
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hernández-Gallegos
authors.forename: Juan
authors.initials: J
authors.lastname: Soriano-Rosas
authors.forename: Julio Isael
authors.initials: JI
authors.lastname: Pérez-Carreón
authors.forename: Javier
authors.initials: J
authors.lastname: Camacho
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism*; D061346:Laser Capture Microdissection; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015221:Potassium Channels; D015222:Sodium Channels; C114462:multidrug resistance-associated protein 3
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