Epstein-Barr virus (EBV) genome and expression in breast cancer tissue:: Effect of EBV infection of breast cancer cells on resistance to paclitaxel (taxol)

Epstein-Barr virus (EBV) genome and expression in breast cancer tissue:: Effect of EBV infection of breast cancer cells on resistance to paclitaxel (taxol)
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DOI:
10.1128/jvi.80.2.845-853.2006
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发表时间:
2006-01-01
影响因子:
5.4
通讯作者:
Joab, I
Joab, I
中科院分区:
医学2区
文献类型:
--
作者:
Arbach, H;Viglasky, V;Joab, I

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爱泼斯坦-巴尔病毒(EBV)已经在乳腺癌的亚型中被检测到。为了阐明这些观察结果,我们用实时定量聚合酶链式反应(Q-PCR)对乳腺癌组织活检标本和显微解剖分离的肿瘤细胞中的EBV基因组进行了量化。我们的发现表明,通过Q-PCR可以在大约一半的肿瘤标本中检测到EBV基因组,通常拷贝数较低。然而,我们也发现,不同肿瘤之间的病毒载量是高度不同的。此外,EBV基因组在形态相同的肿瘤细胞中分布不均,一些分离的肿瘤细胞群含有相对较高的基因组数量,而从同一标本中分离的其他肿瘤细胞可能为EBV DNA阴性。利用逆转录-聚合酶链式反应,我们在几乎所有EBV阳性的肿瘤中检测到EBV基因转录本:EBNA-1,在被分析的一小部分组织中检测到EBV癌蛋白LMP-1的RNA。此外,在所研究的病例中,有一半的病例检测到Barf-1RNA。此外,我们观察到,在体外,乳腺癌细胞的EBV感染使其对紫杉醇(紫杉醇)产生耐药性,并刺激多药耐药基因(Mdr1)的过度表达。因此,即使一小部分乳腺癌细胞被EBV感染,EBV感染对抗癌治疗效率的影响也可能是重要的。
The Epstein-Barr virus (EBV) has been detected in subsets of breast cancers. In order to elaborate on these observations, we quantified by real-time PCR (Q-PCR) the EBV genome in biopsy specimens of breast cancer tissue as well as in tumor cells isolated by microdissection. Our findings show that EBV genomes can be detected by Q-PCR in about half of tumor specimens, usually in low copy numbers. However, we also found that the viral load is highly variable from tumor to tumor. Moreover, EBV genomes are heterogeneously distributed in morphologically identical tumor cells, with some clusters of isolated tumor cells containing relatively high genome numbers while other tumor cells isolated from the same specimen may be negative for EBV DNA. Using reverse transcription-PCR, we detected EBV gene transcripts: EBNA-1 in almost all of the EBV-positive tumors and RNA of the EBV oncoprotein LMP-1 in a smaller subset of the tissues analyzed. Moreover, BARF-1 RNA was detected in half of the cases studied. Furthermore, we observed that in vitro EBV infection of breast carcinoma cells confers resistance to paclitaxel (taxol) and provokes overexpression of a multidrug resistance gene (MDR1). Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance.