Expression of organic cation transporter SLC22A16 in human endometria
Expression of organic cation transporter SLC22A16 in human endometria
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DOI：
10.1097/01.pgp.0000225845.67245.b3
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发表时间：
2007-01-01
影响因子：
2.4
通讯作者：
Yaegashi, Nobuo
中科院分区：
文献类型：
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作者：
Sato, Naoko;Ito, Kiyoshi;Yaegashi, Nobuo
SLC22A16是一种新分离的有机阳离子转运蛋白，负责将阿霉素摄取并转运至细胞内。阿霉素是治疗子宫内膜癌的关键药物之一。因此，我们检测了 SLC22A16 在人子宫内膜及其疾病中的表达。采用免疫组织化学分析和逆转录聚合酶链反应检测 124 例子宫内膜癌标本、25 例正常子宫内膜组织样本（15 例增殖期，10 例分泌期）和 7 例子宫内膜癌细胞系中 SLC22A16 的蛋白和 mRNA 表达水平。还检查了黄体酮暴露后 SLC22A16 mRNA 表达水平的变化。免疫组化分析显示，SLC22A16蛋白在正常分泌期子宫内膜中高表达，但在增殖期其水平显着降低。在 124 个子宫内膜癌标本中的 59 个 (48%) 和 7 个子宫内膜癌细胞系中的 3 个 (43%) 中检测到 SLC22A16 蛋白。通过定量逆转录聚合酶链反应测量的 mRNA 水平与蛋白质表达水平相当。此外，在孕酮存在的情况下，子宫内膜癌细胞系中的 SLC22A16 mRNA 水平增加。总之，SLC22A16在多种子宫内膜组织中表达。其表达水平在分泌期较高，并且可能受到孕激素的调节。我们的研究结果还表明，使用孕激素可能会增加表达 SLC22A16 的子宫内膜样子宫内膜癌对基于阿霉素的化疗方案的反应。
SLC22A16 is one of newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is one of the key drugs for treatment of endometrial cancer. Therefore, we examined expression of SLC22A16 in human endometrium and its disorders. Protein and mRNA expression levels of SLC22A16 were examined in 124 endometrial cancer specimens, 25 normal endometrial tissue samples (15 in proliferative phase, 10 in secretory phase), and 7 endometrial cancer cell lines using immunohistochemical analysis and reverse transcription-polymerase chain reaction. Changes in SLC22A16 mRNA expression level after progesterone exposure were also examined. Immunohistochemical analysis showed that SLC22A16 protein was highly expressed in endometrium during the normal secretory phase, but its level was significantly reduced in the proliferative phase. SLC22A16 protein was detected in 59 of 124 (48%) endometrial cancer specimens and 3 of 7 (43%) endometrial cancer cell lines. The mRNA levels measured by quantitative reverse transcription-polymerase chain reaction were comparable with levels of protein expression. Furthermore, SLC22A16 mRNA levels were increased in endometrial cancer cell lines in the presence of progesterone. In conclusion, SLC22A16 is expressed in various endometrial tissues. Its expression level is high during the secretory phase and may be regulated by progesterone. Our findings also suggest that it may be possible to use progestins to increase the response of endometrioid endometrial carcinoma with SLC22A16 expression to adriamycin-based chemotherapeutic regimens.