Division of Gynaecology, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria.
Gynecol Oncol. 2010 May;117(2):198-201. doi: 10.1016/j.ygyno.2009.10.077. Epub 2009 Nov 17.
ATP-binding Cassette (ABC) transporters are thought to cause multiple drug resistance (MDR) in various carcinomas. Gene expression data from individual transporters in ovarian cancer tissue is contradictory and also scarce for some of them. RNA levels of a panel of ABC transporters were collected and analyzed to get a more detailed overview which transporters are of importance in resistance to chemotherapeutic agents in ovarian carcinoma.
Real-time PCR was used to determine RNA expression levels of 9 ABC transporters in 50 benign tissue samples and 50 recurrent ovarian cancer samples. Genes exhibiting a significant difference between those two groups were further evaluated in 50 primary cancer samples. Data were analyzed with receiver operating characteristic (ROC) curves and multiple Wilcoxon-Mann-Whitney U-tests with Shaffer correction.
Gene expression of four transporters (ABCC1, ABCC2, ABCC3, and ABCB3) was significantly elevated in recurrent cancer lesions compared to benign tissue. Expression levels of these 4 ABC transporters were further analyzed in primary ovarian cancer lesions. A significant difference between primary and recurrent tumor tissue was found in all four genes. Changes in gene expression between benign samples and primary lesions were minor and not relevant.
Four of the examined ABC transporters are likely to play a role in the MDR of ovarian carcinoma. Gene expression of these transporters seems only up regulated through chemotherapy. The thesis that MDR in ovarian cancer is acquired through therapy itself and not present ab initio is supported by these findings.
三磷酸腺苷结合盒(ABC)转运蛋白被认为会导致多种癌症的多药耐药(MDR)。卵巢癌组织中个别转运蛋白的基因表达数据存在矛盾,而且有些数据也很缺乏。本研究收集并分析了一组 ABC 转运蛋白的 RNA 水平,以更详细地了解哪些转运蛋白对卵巢癌化疗药物耐药性具有重要意义。
采用实时 PCR 法测定 50 例良性组织样本和 50 例复发性卵巢癌样本中 9 种 ABC 转运蛋白的 RNA 表达水平。对两组之间存在显著差异的基因进行进一步评估。对 50 例原发性癌症样本进行分析。采用受试者工作特征(ROC)曲线和多个 Wilcoxon-Mann-Whitney U 检验(Shaffer 校正)进行数据分析。
与良性组织相比,四种转运蛋白(ABCC1、ABCC2、ABCC3 和 ABCB3)在复发性癌症病变中的基因表达明显升高。对这四种 ABC 转运蛋白在原发性卵巢癌病变中的表达水平进行了进一步分析。在所有四个基因中,原发性和复发性肿瘤组织之间均存在显著差异。良性样本和原发性病变之间的基因表达变化较小,且无相关性。
四种研究的 ABC 转运蛋白可能在卵巢癌的 MDR 中发挥作用。这些转运蛋白的基因表达似乎仅通过化疗而上调。这些发现支持这样的观点,即卵巢癌中的 MDR 是通过治疗本身获得的,而不是初始存在的。