Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function.

Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function.
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急性髓系白血病中的乳腺癌耐药蛋白(BCRP/MXR/ABCG2):表达与功能之间的不一致。

DOI:
10.1038/sj.leu.2403395
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发表时间:
2004
期刊:
影响因子:
11.4
通讯作者:
Baer,MR
Baer,MR
中科院分区:
医学1区
文献类型:
--
作者:
Suvannasankha,A;Minderman,H;O'Loughlin,KL;Nakanishi,T;Greco,WR;Ross,DD;Baer,MR

文献摘要

相似文献

关于急性髓性白血病(AML)中乳腺癌耐药蛋白(BCRP、MXR、ABCG 2)表达的数据不一致,可能是由于不同研究中使用了不同的检测方法。在8种细胞系和31例AML患者的预处理原始细胞中,通过逆转录聚合酶链反应和流式细胞术研究BCRP mRNA和BCRP蛋白表达(BXP-21、BXP-34或抗ABCG 2抗体,以及抗CD 34和抗CD 33)和功能(烟曲霉素C对米托蒽醌滞留的调节)。BCRP mRNA水平、抗体染色和功能在细胞系中密切相关(Pearson r值,0.73-0.97),但在AML样本中不相关。AML样本中BCRP mRNA水平除1例外均在亲本8226和35倍米托蒽醌耐药8226/MR 20细胞中,且所有BCRP mRNA均在密码子482处具有野生型序列。在AML中,与细胞系不同,BCRP蛋白表达或功能(如果存在)仅在小的亚群中检测到。BCRP mRNA和蛋白表达不相关,不同BCRP抗体染色也不相关,功能与mRNA和蛋白表达均不相关。BCRP仅存在于亚群中,BCRP测量值之间的不一致性表明AML中BCRP的生物学复杂,细胞系建模不完整。
Data on breast cancer resistance protein (BCRP, MXR, ABCG2) expression in acute myeloid leukemia (AML) have been inconsistent, possibly due to use of different assays in different studies. BCRP mRNA was studied by the reverse-transcription polymerase chain reaction and BCRP protein expression (BXP-21, BXP-34 or anti-ABCG2 antibody, with anti-CD34 and anti-CD33) and function (fumitremorgin C modulation of mitoxantrone retention) by flow cytometry in eight cell lines and in pretreatment blasts from 31 AML patients. BCRP mRNA levels, antibody staining and function correlated strongly in cell lines (Pearson r values, 0.73–0.97), but not in AML samples. AML sample BCRP mRNA levels were between those in parental 8226 and 35-fold mitoxantrone-resistant 8226/MR20 cells in all but one case, and BCRP mRNA had the wild-type sequence at codon 482 in all. In AML, unlike in cell lines, BCRP protein expression or function, when present, was only detected in small subpopulations. BCRP mRNA and protein expression did not correlate, nor did staining with different BCRP antibodies, and function did not correlate with mRNA nor protein expression. Presence of BCRP only in subpopulations and discordance among BCRP measurements suggest complex biology of BCRP in AML and incomplete modeling by cell lines.