Sato Naoko, Ito Kiyoshi, Onogawa Toru, Akahira Jun-Ichi, Unno Michiaki, Abe Takaaki, Niikura Hitoshi, Yaegashi Nobuo
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Int J Gynecol Pathol. 2007 Jan;26(1):53-60. doi: 10.1097/01.pgp.0000225845.67245.b3.
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.
溶质载体家族22成员16（SLC22A16）是新分离出的有机阳离子转运体之一，负责将阿霉素摄取并转运到细胞内。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在人子宫内膜及其病变中的表达情况。采用免疫组织化学分析和逆转录-聚合酶链反应检测了124例子宫内膜癌标本、25例正常子宫内膜组织样本（增殖期15例，分泌期10例）和7种子宫内膜癌细胞系中SLC22A16的蛋白质和mRNA表达水平。还检测了孕酮暴露后SLC22A16 mRNA表达水平的变化。免疫组织化学分析显示，SLC22A16蛋白在正常分泌期的子宫内膜中高表达，但在增殖期其水平显著降低。在124例子宫内膜癌标本中的59例（48%）和7种子宫内膜癌细胞系中的3例（43%）检测到SLC22A16蛋白。通过定量逆转录-聚合酶链反应测得的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SLC22A16 mRNA水平升高。总之，SLC22A16在各种子宫内膜组织中均有表达。其表达水平在分泌期较高，且可能受孕酮调节。我们的研究结果还表明，使用孕激素可能会增加表达SLC22A16的子宫内膜样腺癌对基于阿霉素的化疗方案的反应。
