维甲酸对人乳腺癌细胞NIS基因表达和摄碘功能的影响  

Effect of 9-cis-retinoic acid on the functional expression of MS gene in cultured human breast cancer cells

作　　者：何小文[1] 吴华[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院核医学科,武汉430030 [2]福建医科大学附属厦门第一医院核医学科

出　　处：《中华核医学杂志》2005年第5期278-281,共4页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金资助项目(30171062)

摘　　要：目的探讨9-顺-维甲酸(9-cis—RA)对人乳腺癌细胞钠/碘同向转运体(NIS)基因功能表达的影响。方法应用9-cis—RA和全反式维甲酸(ATRA)分别在不同浓度下对雌激素受体(ER) 阳性的乳腺癌细胞(MCF-7)和ER阴性的乳腺癌细胞(MDA-MB-231)进行干预,于不同时间点提取细胞总RNA,通过半定量逆转录-聚合酶链反应(RT—PCR)检测乳腺癌细胞NIS mRNA表达水平的变化;在体外培养条件下研究RA刺激后乳腺癌细胞对放射性碘的摄取情况。结果9-cis-RA处理后, MCF-7细胞NIS mRNA表达增强,呈浓度依赖性(F=114.17,P<0.001),在10-6mol/L浓度下NIS mRNA的表达随时间上调,16 h时达到最高,是对照组(0 h)的8.2倍(q=8.32,P<0.01),此后随时间逐渐下调;且9-cis-RA(10-6mol/L,24 h)的作用强于ATRA(t=6.572,P<0.01)。MDA-MB-231 基础状态下几乎无NIS表达,9-cis-RA刺激后可上调其表达(t=20.195,P<0.001),但表达量(NIS/ β-actin)远低于MCF-7(t=10.395,P<0.001)。碘摄取实验表明,10-6mol/L 9-cis-RA干预12 h后。MCF-17细胞摄碘开始增加,干预24 h时碘摄取达最大,是基础状态下的3.2倍.其摄碘能力可被KClO4抑制。结论9-cis—RA能明显增强ER阳性的MCF-7细胞NIS基因的表达及摄碘功能。Objective To investigate the effect of 9-cis-retinoic acid （9-cis-RA） on the functional expression of sodium/iodide symporter （NIS） in cultured human breast cancer cells. Methods Two breast cancer cell lines including estrogen receptor （ER）-positive MCF-7 and ER-negative MDA-MB-231 were incu- bated with different doses （10^-8, 10^-7 or 10^-6 moL/L） of either 9-cis-RA or all-trans-retinoic acid （ATRA） for various durations （0 -44 h）. Total RNA was isolated, and then reverse transcription-polymerase chain reaction （RT-PCR） was performed to measure the expression levels of NIS mRNA. ^131I uptake was determined in breast cancer cells after treated with RA under the same culture condition for expression of NIS transport. Results RT-PCR analysis revealed a dose-dependent induction effect on the expression of NIS mRNA in MCF-7 cells exposed to 9-cis-RA （F = 114. 17, P 〈 0. 001 ）. The maximal up-regulation of NIS mRNA expression appeared at 16 h after treated with 9-cis-RA （ 10^ -6 mol/L） , which was 8.2 times higher than that of control （q = 8.32, P 〈0. O1 ）. Moreover, 9-cis-RA （10^-6 mol/L, 24 h） enhanced NIS mRNA expression more effectively than ATRA （t =6. 572, P 〈0.01 ）. No expression of NIS mRNA was detected in untreated MDA-MB-231 cells; however, unregulated NIS mRNA expression was induced after incubation with 9-cis-RA （10^-6 mol/L） but the expression was far lowered than MCF-7 （t = 20. 195, P 〈 0.001 ）. As to the ^131I uptakes it increased in MCF-7 cells at 12 h and reached to the maximum at 24 h （ 3.2-fold over that of baseline） after treated with 10^-6 mol/L 9-cis-RA. Also, ^131I uptake could be blocked by 3 × 10^-5 mol/L KClO4, a specific inhibitor of NIS. Conclusion 9-cis-RA can significantly enhance the functional expression of NIS and increase the uptake of ^131I in ER-positive MCF-7 human breast cancer cells.

关 键 词：乳腺肿瘤 肿瘤细胞 培养的 基因表达 维甲酸 聚合酶链反应 人乳腺癌细胞 9-顺-维甲酸 NIS基因 摄碘功能 半定量逆转录-聚合酶链反应 

分 类 号：R737.9[医药卫生—肿瘤] R979.1[医药卫生—临床医学]