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

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

Volume: 12 Issue: 1

Author(s): Khondoker Alam, Taleah Farasyn, Kai Ding and Wei Yue*

Affiliation:

• Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK,United States

Keywords: Organic anion transporting polypeptide (OATP) 1B3, mRNA, transport protein, cancer, ovary, prostate, bladder, breast, lung.

Abstract: 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.

Cite this article as:

Alam Khondoker, Farasyn Taleah, Ding Kai and Yue Wei*, Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues, Drug Metabolism Letters 2018; 12 (1) . https://dx.doi.org/10.2174/1872312812666180326110146