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      Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues

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          Abstract

          Background

          Membrane transport protein organic anion transporting polypeptide (OATP) 1B3 mediates the cellular uptake of many drugs including anti-cancer drugs (e.g. paclitaxel). In addition to the well-recognized hepatic expression and function of OATP1B3 [herein named liver-type (Lt) OATP1B3], OATP1B3 also expresses in cancers and has been postulated to play a role in cancer therapy presumably by facilitating the influx of anti-cancer drugs. Recently, a cancer type (Ct)-OATP1B3 mRNA variant was identified in colon and lung cancer tissues, which encodes truncated Ct-OATP1B3 with negligible transport activity. Other than colon and lung cancers, reports on mRNA expression of OATP1B3 in other cancers cannot distinguish between the Lt- and Ct-OATP1B3.

          Objective

          The current studies were designed to characterize the expression of Lt- and Ct-OATP1B3 mRNA in ovarian, prostate, bladder, breast, and lung tissues.

          Methods

          Lt- and Ct-OATP1B3 isoform-specific PCR primers were utilized to determine the mRNA levels of Lt- and Ct-OATP1B3, respectively. An expression vector expressing green fluorescent protein (GFP)-tagged Lt-OATP1B3 was transiently transfected into the ovarian cancer cell line SKOV3. Confocal live-cell microscopy was utilized to determine the localization of GFP-Lt-OATP1B3 in SKOV3 cells.

          Results

          For the first time, Lt-OATP1B3 mRNA was detected in ovarian, prostate, bladder and breast cancers. The GFP-Lt-OATP1B3 expressed in the ovarian cancer cell line SKOV3 has a plasma membrane localization pattern as shown by confocal microscopy.

          Conclusion

          Our findings are supportive of the potential role of Lt-OATP1B3 in cancer therapy.

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          Author and article information

          Journal
          101313587
          35731
          Drug Metab Lett
          Drug Metab Lett
          Drug metabolism letters
          1872-3128
          1874-0758
          8 June 2018
          2018
          01 January 2019
          : 12
          : 1
          : 24-32
          Affiliations
          [a ]Department of Pharmaceutical Sciences, Wei Yue, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
          [b ]Department of Biostatistics and Epidemiology, Kai Ding, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
          Author notes
          [* ] Corresponding author: Wei Yue, Current address: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center College of Pharmacy, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117. Phone: (405) 271-6593 Ext. 47828, Fax: (405) 271-7505, wei-yue@ 123456ouhsc.edu
          Article
          PMC6133766 PMC6133766 6133766 nihpa973538
          10.2174/1872312812666180326110146
          6133766
          29577869
          7cf2898a-e21b-4730-9aea-873f331b7e69
          History
          Categories
          Article

          Lung,Breast,Bladder,Prostate,Ovary,Cancer,transport protein,mRNA,Organic anion transporting polypeptide (OATP) 1B3

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