title: Different regulation of P-glycoprotein function between Caco-2 and Caki-1 cells by ezrin, radixin and moesin proteins.
abstract: OBJECTIVE
  P-glycoprotein (P-gp) mediates efflux of many xenobiotics, including therapeutic drugs, from normal and tumour tissues, and its functional localization on the plasma membrane of cells is regulated by scaffold proteins, such as ezrin, radixin and moesin (ERM proteins). We previously reported that radixin is involved in post-translational regulation of P-gp in hepatocellular carcinoma HepG2 cells and mouse small intestine, but not in mouse kidney.
  
  
  METHODS
  Here, we investigated whether the role of ERM proteins in regulation of P-gp transport activity in cancers is the same as that in the corresponding normal tissues, using human colon adenocarcinoma (Caco-2) cells and renal carcinoma (Caki-1) cells.
  
  
  RESULTS
  In Caco-2 cells, radixin silencing alone reduced the P-gp-mediated intracellular accumulation of rhodamine123 (Rho123), while the mRNA level of P-gp was unchanged. Thus, it appears that only radixin among the ERMs regulates P-gp activity in Caco-2 cells. On the other hand, none of the ERM proteins influenced P-gp activity in Caki-1 cells.
  
  
  CONCLUSIONS
  The regulation of P-gp by ERM proteins is different between Caco-2 and Caki-1 cells. Moreover, these regulatory properties are the same as those of the corresponding normal tissues, and suggest that tissue-specific differences in the regulation of P-gp by ERM proteins are retained in cancerous tissues.
authors.affiliation: Laboratory of Biopharmaceutics, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yano
authors.affiliation: Laboratory of Biopharmaceutics, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Kyoma
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Laboratory of Biopharmaceutics, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Biopharmaceutics, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kawabata
authors.affiliation: Laboratory of Molecular Pathophysiology, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohmori
authors.affiliation: Laboratory of Biopharmaceutics, Department of Pharmacology, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D018938:Caco-2 Cells; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000099149:Ezrin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000099149:Ezrin; C071058:moesin; C071776:radixin
keywords: P-gp transport activity; intestinal cancer; radixin; renal cancer; tissue differences