title: Unique expression features of cancer-type organic anion transporting polypeptide 1B3 mRNA expression in human colon and lung cancers.
abstract: BACKGROUND
  We have previously identified the cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) mRNA in several human colon and lung cancer tissues. Ct-OATP1B3 is a variant of the liver-type OATP1B3 (Lt-OATP1B3) mRNA, which is a hepatocyte plasma membrane transporter with broad substrate specificity. However, in cancer tissues, both the detailed characteristics of Ct-OATP1B3 mRNA expression and its biological functions remain unclear. With this point in mind, we sought to characterize Ct-OATP1B3 mRNA expression in colon and lung cancer tissues. In addition, we attempted to obtain functional implication of Ct-OATP1B3 in cancer cells.
  
  
  METHODS
  Matched pairs of cancer and normal tissues were collected from 39 colon cancer and 28 lung cancer patients. The OATP1B3 mRNA expression levels in each of these tissues were separately determined by quantitative real-time polymerase chain reaction. Mann-Whitney U test and Fisher's exact test were used in statistical analysis. The Ct-OATP1B3 functional expression in colon cancer cells was then examined by Western blotting and transport analyses.
  
  
  RESULTS
  Ct-OATP1B3 mRNA, but not Lt-OATP1B3 mRNA, was abundantly expressed in colon cancer tissues at a higher detection frequency (87.2%) than that of the adjacent normal tissues (2.6%). Furthermore, it was found that Ct-OATP1B3 mRNA expression was often detected in early colon cancer stages (88.9%, n = 18), and that its expression was associated with well-differentiated colon cancer statuses. On the other hand, Ct-OATP1B3 mRNA also showed a predominant and cancer-associated expression profile in lung tissues, although at frequencies and expression levels that were lower than those obtained from colon cancer. As for attempts to clarify the Ct-OATP1B3 functions, neither protein expression nor transport activity could be observed in any of the cell lines examined.
  
  
  CONCLUSIONS
  Based on the unique characteristics of the Ct-OATP1B3 mRNA expression profile identified in this study, Ct-OATP1B3 mRNA can be expected to become a biomarker candidate for use in colon (and lung) cancer diagnosis. Simultaneously, our results advance the possibility that Ct-OATP1B3 might play yet unidentified roles, in addition to transporter function, in cancer cell biology.
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Furihata
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Harada
authors.affiliation: Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimozato
authors.affiliation: Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kamijo
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamiichi
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba-shi 260-8675, Chiba, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Chiba
keywords: Cancer biomarker; Cancer-specific expression; Colon cancer; Lung cancer; OATP1B3; SLCO1B3; Transporter