Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma

Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine, Sendai 2980-8574, Japan.
Cancer Science (Impact Factor: 3.52). 11/2007; 98(10):1570-6. DOI: 10.1111/j.1349-7006.2007.00570.x
Source: PubMed


Human liver-specific organic anion transporter-2 (LST-2/OATP8/SLCO1B3) has been demonstrated to be expressed in various gastrointestinal carcinomas and also to play pivotal roles in the uptake of a wide variety of both endogenous and exogenous anionic compounds, including bile acids, conjugated steroids and hormones, into hepatocytes in the human liver. However, the biological significance of LST-2 in human carcinomas remains unknown. In the present study, we examined the expression of LST-2 in 102 cases of breast carcinoma using immunohistochemistry and correlated the findings with various clinicopathological parameters in order to examine the possible biological and clinical significance of LST-2. LST-2 immunoreactivity was detected in 51 cases (50.0%); of these 51 positive cases, LST-2 immunoreactivity was inversely correlated with tumor size (P = 0.0289). In addition, LST-2 immunoreactivity was significantly associated with a decreased risk of recurrence and improved prognosis by both univariate (P = 0.02 and P = 0.01) and multivariate (P = 0.03 and P = 0.01) analyses. In the estrogen receptor-positive groups, the LST-2-positive patients showed good prognoses. Considering that LST-2 transports estrone-3-sulfate, these results suggest that LST-2 overexpression is associated with a hormone-dependent growth mechanism of the breast cancer. The results of our present study demonstrate that LST-2 immunoreactivity is a potent prognostic factor in human breast cancer.

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Available from: Michiaki Unno, Oct 08, 2014
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    • "Therefore , we used RTMs containing the clinically evaluated HSVtk-GCV system (Immonen et al., 2004; Nasu et al., 2007; Schwarzenberger et al., 2011; Xu et al., 2009). In a doubletransfection system, we analyzed RTMs targeting the solute carrier organic anion transporter family member 1B3 (SLCO1B3), a marker gene associated with various human cancers , including colorectal adenocarcinomas (Lee et al., 2008), breast (Muto et al., 2007) and lung cancer (Nagai et al., 2012) and, most importantly for our purposes, RDEB-SCC (Cole et al., 2009). Here we describe a suicide-RTM screening system which provides information on the ability of individual RTMs to induce tumor-specific cell death. "
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    ABSTRACT: Targeting tumor marker genes by RNA trans-splicing is a promising means to induce tumor cell-specific death. Using a screening system we designed RNA trans-splicing molecules (RTM) specifically binding the pre-mRNA of SLCO1B3, a marker gene in epidermolysis bullosa associated squamous cell carcinoma (EB-SCC). Specific trans-splicing, results in the fusion of the endogenous target mRNA of SLCO1B3 and the coding sequence of the suicide gene, provided by the RTM. SLCO1B3-specific RTMs containing HSV-tk were analyzed regarding their trans-splicing potential in a heterologous context using a SLCO1B3 expressing minigene (SLCO1B3-MG). Expression of the chimeric SLCO1B3-tk was detected by semi-quantitative RT-PCR and Western blot analysis. Cell viability and apoptosis assays confirmed that the RTMs induced suicide gene-mediated apoptosis in SLCO1B3-MG expressing cells. The lead RTM also showed its potential to facilitate a trans-splicing reaction into the endogenous SLCO1B3 pre-mRNA in EB-SCC cells resulting in tk-mediated apoptosis. We assume that the pre-selection of RTMs by our inducible cell-death system accelerates the design of optimal RTMs capable to induce tumor specific cell death in skin cancer cells.
    Molecular oncology 08/2013; 7(6). DOI:10.1016/j.molonc.2013.08.005 · 5.33 Impact Factor
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    • "Organic anion transporting polypeptide 1B3 (OATP1B3) belongs to the superfamily of OATP transporters and mediates the hepatic uptake of various endogenous and xenobiotic compounds [1]. Although OATP1B3 was initially considered to be a liver-specific transporter, subsequent investigations revealed that OATP1B3 is also expressed in human cancers derived from multiple organs including colon, pancreas, prostate, breast and lung [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]. "
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    Biochemical pharmacology 08/2013; 86(6). DOI:10.1016/j.bcp.2013.07.020 · 5.01 Impact Factor
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    • "y Kalliokoski and Niemi ( 2009 ) and Konig ( 2011 ) . Many cancer tissues and cell lines have altered expression of OATPs . For example , the normally liver - exclusive OATP1B3 is also expressed in gastric , colon and pancreatic cancers ( Abe et al . , 2001 ; Lee et al . , 2008 ) , as well as cancers of the lung ( Monks et al . , 2007 ) , breast ( Muto et al . , 2007 ) and prostate ( Hamada et al . , 2008 ) , whereas it has a reduced expression in hepatocellular carcinomas ( Kinoshita and Miyata , 2002 ; Cui et al . , 2003 ; Vavricka et al . , 2004 ) . Similarly , most of the other OATPs have been shown to have altered expression in different types of cancers . Because OATPs are known to transport h"
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    ABSTRACT: The human organic anion and cation transporters are classified within two SLC superfamilies. Superfamily SLCO (formerly SLC21A) consists of organic anion transporting polypeptides (OATPs), while the organic anion transporters (OATs) and the organic cation transporters (OCTs) are classified in the SLC22A superfamily. Individual members of each superfamily are expressed in essentially every epithelium throughout the body, where they play a significant role in drug absorption, distribution and elimination. Substrates of OATPs are mainly large hydrophobic organic anions, while OATs transport smaller and more hydrophilic organic anions and OCTs transport organic cations. In addition to endogenous substrates, such as steroids, hormones and neurotransmitters, numerous drugs and other xenobiotics are transported by these proteins, including statins, antivirals, antibiotics and anticancer drugs. Expression of OATPs, OATs and OCTs can be regulated at the protein or transcriptional level and appears to vary within each family by both protein and tissue type. All three superfamilies consist of 12 transmembrane domain proteins that have intracellular termini. Although no crystal structures have yet been determined, combinations of homology modelling and mutation experiments have been used to explore the mechanism of substrate recognition and transport. Several polymorphisms identified in members of these superfamilies have been shown to affect pharmacokinetics of their drug substrates, confirming the importance of these drug transporters for efficient pharmacological therapy. This review, unlike other reviews that focus on a single transporter family, briefly summarizes the current knowledge of all the functionally characterized human organic anion and cation drug uptake transporters of the SLCO and the SLC22A superfamilies.
    British Journal of Pharmacology 03/2012; 165(5):1260-87. DOI:10.1111/j.1476-5381.2011.01724.x · 4.84 Impact Factor
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