The expression profile of ATP-binding cassette transporter genes in breast carcinoma
The expression profile of ATP-binding cassette transporter genes in breast carcinoma
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DOI：
10.2217/pgs.13.26
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发表时间：
2013-04-01
期刊：
影响因子：
2.1
通讯作者：
Soucek, Pavel
中科院分区：
文献类型：
--
作者：
Hlavac, Viktor;Brynychova, Veronika;Soucek, Pavel
目的：ATP结合盒（ABC）转运蛋白通过ATP依赖性药物外排参与肿瘤耐药的发生。我们研究的一个主要目的是调查ABC转运蛋白的表达与乳腺癌患者预后之间的关系。患者和方法：在来自68名通过新辅助化疗治疗的乳腺癌患者的治疗后肿瘤和非肿瘤组织样品中测定所有49种人ABC转运蛋白的转录水平。然后在100例治疗前患者的独立系列中评价6种ABC转运蛋白。结果如下：与非肿瘤组织相比，治疗后肿瘤中ABCA 5/6/8/9/10、ABCB 1/5/11、ABCC 6/9、ABCD 2/4、ABCG 5和ABCG 8显著下调，ABCA 2/3/7/12、ABCB 2/3/8/9/10、ABCC 1/4/5/10/11/12、ABCD 1/3、ABCE 1、ABCF 1/2/3和ABCG 1上调。在两组患者中均发现肿瘤内ABCC 1和ABCC 8水平与激素受体的分级和表达显著相关。ABCA 12、ABCA 13和ABCD 2水平与治疗后患者对新辅助化疗的反应显著相关。应用免疫印迹技术首次观察了乳腺癌组织中ABCA 12、ABCC 8和ABCD 2的蛋白表达。结论：ABCA 12、ABCA 13、ABCC 1、ABCC 8和ABCD 2可能是乳腺癌进展和化疗反应的调节因子。
Aim: ATP-binding cassette (ABC) transporters contribute to development of resistance to anticancer drugs via ATP-dependent drug efflux. A major goal of our study was to investigate associations between the expression of ABC transporters and outcome of breast carcinoma patients. Patients & methods: Transcript levels of all 49 human ABC transporters were determined in post-treatment tumor and non-neoplastic tissue samples from 68 breast carcinoma patients treated by neoadjuvant chemotherapy. Six ABC transporters were then evaluated in independent series of 100 pretreatment patients. Results: ABCA5/6/8/9/10, ABCB1/5/11, ABCC6/9, ABCD2/4, ABCG5 and ABCG8 were significantly downregulated and ABCA2/3/7/12, ABCB2/3/8/9/10, ABCC1/4/5/10/11/12, ABCD1/3, ABCE1, ABCF1/2/3 and ABCG1 were upregulated in post-treatment tumors compared with non-neoplastic tissues. Significant associations of intratumoral levels of ABCC1 and ABCC8 with grade and expression of hormonal receptors were found in both sets of patients. ABCA12, ABCA13 and ABCD2 levels were significantly associated with the response to neoadjuvant chemotherapy in post-treatment patients. Protein expression of ABCA12, ABCC8 and ABCD2 in tumor tissues of patients with breast carcinoma was observed by immunoblotting for the first time. Conclusion: ABCA12, ABCA13, ABCC1, ABCC8 and ABCD2 present potential modifiers of progression and response to the chemotherapy of breast carcinoma.