Differential expression of the polyspecific drug transporter OCT1 in rat hepatocarcinoma cells.
The polyspecific drug transporter OCT1 is a plasma transmembrane protein involved in the uptake of cationic drugs into hepatocytes. In order to determine whether hepatic OCT1 levels, like those of the other cationic drug transporter P-glycoprotein, may be altered during hepatocarcinogenesis, we have investigated OCT1 expression and activity in rat liver carcinoma cells. Similar levels of OCT1 mRNAs were evident in both normal liver and diethylnitrosamine-induced hepatocarcinomas by Northern blot analysis. In contrast, five hepatoma cell lines (Fao, Faza, H5, HTC and RHC1) showed either a decrease or an absence of OCT1 expression compared to normal hepatocytes; these hepatoma cells also displayed lower intracellular accumulation of tetraethylammonium (TEA), a well-known substrate for OCT1. However, among the hepatoma cell lines, the well-differentiated Fao cell line was found to retain substantial levels of OCT1 expression and of intracellular TEA uptake. Therefore, these data provide the first evidence that OCT1 expression is well-preserved in chemically-induced rat malignant neoplastic liver lesions, whereas it is either decreased or undetectable in hepatoma cell lines, which may be related to the loss of various liver functions usually occurring in these cell lines.
Lecureur
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V
INSERM U456, Détoxication et Réparation Tissulaire, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France.
Guillouzo
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A
Fardel
O
O
D000818:Animals; D001692:Biological Transport; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004052:Diethylnitrosamine; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019789:Tetraethylammonium / Q000493:pharmacokinetics
D002273:Carcinogens; D002352:Carrier Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D019789:Tetraethylammonium