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Clinical application of the origanic anion transporter family

有机阴离子转运蛋白家族的临床应用

基本信息

批准号：
18390045
负责人：
ABE Takaaki
金额：
$ 10.82万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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, so far, the biological significance of LST-2 in human carcinomas remains unknown.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 and multivariate 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.

人肝特异性有机阴离子转运蛋白2（LST-2/OATP 8/SLCO 1B 3）在多种胃肠道肿瘤中表达，并在人肝细胞对胆汁酸、结合类固醇和激素等多种内源性和外源性阴离子化合物的摄取中发挥关键作用。然而，到目前为止，LST-2在人类肿瘤中的生物学意义仍然未知，我们研究了LST-2在102例乳腺癌中的表达，采用免疫组织化学方法，并将结果与各种临床病理参数相关联，以检查LST-2可能的生物学和临床意义。LST-2免疫反应阳性51例（50.0%），这51例阳性病例中，LST-2免疫反应与肿瘤大小呈负相关（P=0.0289）。此外，单变量和多变量分析显示，LST-2免疫反应性与复发风险降低和预后改善显著相关。在雌激素受体阳性组中，LST-2阳性患者表现出良好的预后。考虑到LST-2转运雌酮-3-硫酸酯，这些结果表明LST-2过表达与乳腺癌的乳腺癌依赖性生长机制相关。我们目前的研究结果表明，LST-2免疫反应性是一个强有力的预后因素，在人类乳腺癌。