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

Tohoku University, Sendai-shi, Miyagi, 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.
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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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    • "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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