Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues.
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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DOI：
10.2174/1872312812666180326110146
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发表时间：
2018
影响因子：
--
通讯作者：
Yue W
中科院分区：
文献类型：
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作者：
Alam K;Farasyn T;Ding K;Yue W
膜转运蛋白有机阴离子转运多肽 (OATP) 1B3 介导许多药物的细胞摄取，包括抗癌药物（例如紫杉醇）。除了众所周知的 OATP1B3 [本文称为肝型 (Lt) OATP1B3] 的肝脏表达和功能之外，OATP1B3 也在癌症中表达，并且推测其在癌症治疗中发挥作用，推测是通过促进抗癌药物的流入。最近，在结肠癌和肺癌组织中发现了一种癌症型 (Ct)-OATP1B3 mRNA 变体，其编码截短的 Ct-OATP1B3，其转运活性可忽略不计。除结肠癌和肺癌外，其他癌症中 OATP1B3 mRNA 表达的报道无法区分 Lt-OATP1B3 和 Ct-OATP1B3。目前的研究旨在表征卵巢、前列腺、膀胱、乳腺和肺组织中 Lt-和 Ct-OATP1B3 mRNA 的表达。利用 Lt- 和 Ct-OATP1B3 同种型特异性 PCR 引物分别测定 Lt- 和 Ct-OATP1B3 的 mRNA 水平。将表达绿色荧光蛋白 (GFP) 标记的 Lt-OATP1B3 的表达载体瞬时转染至卵巢癌细胞系 SKOV3 中。利用共聚焦活细胞显微镜确定 GFP-Lt-OATP1B3 在 SKOV3 细胞中的定位。首次在卵巢癌、前列腺癌、膀胱癌和乳腺癌中检测到 Lt-OATP1B3 mRNA。共聚焦显微镜显示，卵巢癌细胞系 SKOV3 中表达的 GFP-Lt-OATP1B3 具有质膜定位模式。我们的研究结果支持 Lt-OATP1B3 在癌症治疗中的潜在作用。
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. The current studies were designed to characterize the expression of Lt- and Ct-OATP1B3 mRNA in ovarian, prostate, bladder, breast, and lung tissues. 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. 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. Our findings are supportive of the potential role of Lt-OATP1B3 in cancer therapy.