Khondoker Alam, Taleah Farasyn, Kai Ding and Wei Yue* Pages 24 - 32 ( 9 )
Background: Membrane transport protein organic anion transporting polypeptide (OATP) 1B3 mediates the cellular uptake of many clinically important 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 in colon and lung cancers, reports on mRNA expression of OATP1B3 in other cancers cannot distinguish between the Ltand 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 localization of GFP-Lt-OATP1B3 on the plasma membrane of SKOV3 cells after transient transfection was readily detected by confocal microscopy.
Conclusion: Our findings are supportive of the potential role of Lt-OATP1B3 in cancer cells.
Organic anion transporting polypeptide (OATP) 1B3, mRNA, transport protein, cancer, ovary, prostate, bladder, breast, lung.
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK