Function and role for organic anion transporter expressed in gastrointestinal and breast cancer

有机阴离子转运蛋白在胃肠道癌和乳腺癌中表达的功能和作用

• 批准号: 17390358
• 负责人: UNNO Michiaki
• 金额: $ 10.66万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390358/
• 关键词: Organic Anino transporter; Breast caner; Colon cancer; Prognostic factor; トランスレーショナルリサーチ; 癌; 外科; 生体分子; トランスポーター; LST-2; 結腸癌; 予後因子; 免疫組織化学

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 or present study demonstrate that LST-2 immunoreactivity is a potent prognostic factor in human breast cancer.

人类肝脏特异性有机阴离子转运蛋白-2 （LST-2/OATP8/SLCO1B3）已被证明在多种胃肠道癌中表达，并在多种内源性和外源性阴离子化合物（包括胆汁酸、偶联类固醇和激素）摄取到人类肝脏的肝细胞中发挥关键作用。然而，LST-2在人类肿瘤中的生物学意义尚不清楚。在本研究中，我们采用免疫组织化学方法检测了LST-2在102例乳腺癌中的表达，并将其与各种临床病理参数相关联，以探讨LST-2可能的生物学和临床意义。51例（50.0%）检测到LST-2免疫反应性；在51例阳性病例中，LST-2免疫反应性与肿瘤大小呈负相关（P=0.0289）。此外，单因素（P=0.02和P=0.01）和多因素（P=0.03和P=0.01）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阳性患者预后良好。考虑到LST-2转运硫酸雌酮3，这些结果提示LST-2过表达与乳腺癌激素依赖性生长机制有关。目前的研究结果表明，LST-2免疫反应性是人类乳腺癌的一个强有力的预后因素。

项目成果

Farnesoid X receptor, hepatocytes nuclear factor 1 α and 3 β are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene

Farnesoid X 受体、肝细胞核因子 1 α 和 3 β 对于肝脏特异性有机阴离子转运蛋白 2 基因的转录激活至关重要

• 发表时间: 2006
• 期刊: J Gastroenterology 41
• 作者: Ohtsuka H;et al.
• 通讯作者: et al.

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

• DOI: 10.1111/j.1349-7006.2007.00570.x
• 发表时间: 2007-10-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Muto, Mitsuhisa;Onogawa, Tohru;Unno, Michiaki
• 通讯作者: Unno, Michiaki

Expression of organic cation transporter SLC22A16 in human endometria

• DOI: 10.1097/01.pgp.0000225845.67245.b3
• 发表时间: 2007-01-01
• 期刊: INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
• 影响因子: 2.4
• 作者: Sato, Naoko;Ito, Kiyoshi;Yaegashi, Nobuo
• 通讯作者: Yaegashi, Nobuo

CDHPとsiRNAによるDPD阻害後のヒト膵癌細胞株の5-FUに対する化学感受性

CDHP 和 siRNA 抑制 DPD 后人胰腺癌细胞系对 5-FU 的化学敏感性

• 发表时间: 2007
• 作者: Kikuchi S;Ikehira H;et al.;石田晶玄
• 通讯作者: 石田晶玄

肝門部胆管癌に対する右肝動脈合併切除・再建を伴う肝左様切除

左肝切除联合右肝动脉切除重建治疗肝门部胆管癌

• 发表时间: 2007
• 期刊: 消化器外科 30(7)
• 作者: Higashimoto;M;海野 倫明
• 通讯作者: 海野 倫明