Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer
Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer
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DOI：
10.1016/j.bbrc.2006.02.172
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发表时间：
2006-05-05
影响因子：
3.1
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Gupta, N;Martin, PM;Ganapathy, V
乳腺癌耐药蛋白（BCRP/ABCG2）在肿瘤细胞中的表达与多种化疗药物的耐药有关。BCRP还通过介导原卟啉从细胞外排来防止光毒性。然而，化疗和光动力疗法是治疗癌症的有效选择。此外，原卟啉以血红素的形式对一氧化氮的合成至关重要，而一氧化氮的过量产生与癌症有关。这就提出了一个问题，即这种转运蛋白的表达是否在癌症中发生了改变。为了解决这个问题，我们研究了BCRP在结直肠癌和宫颈癌中的表达。取结肠切除术标本配对的正常组织和癌组织，采用RT-PCR和Northern blot分析BCRP mRNA。免疫组织化学/免疫荧光法分析BCRP。对正常子宫颈和癌子宫颈标本也进行了类似的研究。采用商业点印迹法对154例肿瘤患者19种不同组织的正常和癌cDNA配对样本中BCRP的表达进行了定量检测。BCRP mRNA在正常结直肠组织中存在，在癌组织中减少6倍。BCRP在正常结肠中含量丰富，在结肠癌中含量降低。BCRP mRNA和蛋白的下调在宫颈癌中也很明显。从154名患者身上收集的19种不同组织中，有12种BCRP mRNA在癌症中也有所下降。这些数据表明，癌症相关的BCRP下调可能是几种组织中的普遍现象。BCRP表达的降低可能通过允许基因毒素的积累和一氧化氮的过度产生而在肿瘤发生中起作用。(c) 2006爱思唯尔公司版权所有。
Expression of Breast Cancer Resistance Protein (BCRP/ABCG2) in tumor cells is associated with resistance to multiple chemotherapeutic agents. BCRP also protects against phototoxicity by mediating the efflux Of protoporphyrins from cells. However, chemotherapy and photodynamic therapy are effective treatment options for cancer. Furthermore, protoporphyrins are essential, in the form of heme, for the synthesis of nitric oxide, over-production of which is associated with cancer. This raises the question as to whether the expression of this transporter is altered in cancer. To address this question, we investigated the expression of BCRP in colorectal cancer and cervical cancer. Paired normal and cancer tissues from colectomy specimens were used for the analysis of BCRP mRNA by RT-PCR and Northern blot. BCRP was analyzed by immunohistochemistry/immunofluorescence. Similar studies were also done with specimens of normal cervix and cancer cervix. A commercial dot blot was probed to quantify the expression of BCRP in paired normal and cancer cDNA samples from 154 patients with tumors in 19 different tissues. BCRP mRNA was present in normal colorectal tissue and showed a 6-fold decrease in cancer. BCRP was abundant in the normal colon and showed a decrease in colon cancer. The down-regulation of BCRP mRNA and protein was also evident in cervical cancer. There was also a decrease in BCRP mRNA in cancer in 12 of the 19 different tissues collected from 154 patients. These data show that cancer-associated down-regulation of BCRP is likely to be a common phenomenon in several tissues. Decreased expression of BCRP may have a role in tumorigenesis by allowing accumulation of genotoxins and over-production of nitric oxide. (c) 2006 Elsevier Inc. All rights reserved.