Multiple gene expression analysis reveals distinct differences between G2 and G3 stage breast cancers, and correlations of PKC eta with MDR1, MRP and LRP gene expression.
Multiple gene expression analysis reveals distinct differences between G2 and G3 stage breast cancers, and correlations of PKC eta with MDR1, MRP and LRP gene expression.
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DOI：
10.1038/bjc.1998.13
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发表时间：
1998
影响因子：
8.8
通讯作者：
Gekeler, V
中科院分区：
文献类型：
--
作者：
Beck, J;Bohnet, B;Brügger, D;Bader, P;Dietl, J;Scheper, RJ;Kandolf, R;Liu, C;Niethammer, D;Gekeler, V
通过对体外筛选的MDR细胞系的研究，推测蛋白激酶C （PKC）与p糖蛋白（P-gp）介导的多药耐药（MDR）之间可能存在联系。PKC与MDR表型的功能相关性尚不清楚，临床上发生的耐药中特定PKC同工酶的参与尚不清楚。最近，我们在急性髓性白血病（AML）患者和卵巢癌患者的腹水细胞抽吸物中证实了PKC eta同工酶与MDR1或MRP（多药耐药相关蛋白）基因表达水平之间的显著相关性。为了将这些发现扩展到其他类型的人类肿瘤，我们分析了64例原发性乳腺癌患者的标本，通过dna - pcr方法分析了几种耐多药相关基因(MDR1、MRP、LRP（肺癌耐药相关蛋白）、拓扑异构酶（Topo） II α /II β、细胞周期蛋白A和PKC同工酶基因（α、β 1、β 2、β 1、β 2和mu）的个体表达水平。我们发现，与G3相比，G2肿瘤中MRP、LRP和PKC eta基因表达的平均值显著提高，但Topo II α和cyclin A基因表达水平显著降低。值得注意的是，MDR1、MRP或LRP基因表达水平与PKC eta呈显著正相关：MDR1/PKC eta (rs = +0.6451, P < 0.0001) n = 62；MRP/PKC eta (rs = +0.5454, P < 0.0001) n = 63；LRP/PKC eta (rs = +0.5436, P < 0.0001) n = 62；MRP/LRP （rs = +0.7703, P < 0.0001）和n = 62, MDR1/MRP (rs = +0.5042, P < 0.0001) n = 62。我们的研究结果表明，临床中存在多因子耐多药，PKC eta可能是不同类型肿瘤中一系列耐多药相关基因上调的关键调控因子。
A possible link between protein kinase C (PKC) and P-glycoprotein (P-gp)-mediated-multidrug resistance (MDR) was assumed from studies on MDR cell lines selected in vitro. The functional relevance of PKC for the MDR phenotype remains unclear, and the involvement of a particular PKC isozyme in clinically occurring drug resistance is not known. Recently, we have demonstrated significant correlations between the expression levels of the PKC eta isozyme and the MDR1 or MRP (multidrug resistance-associated protein) genes in blasts from patients with acute myelogenous leukaemia (AML) and in ascites cell aspirates from ovarian cancer patients. To extend these findings to further types of human tumours we analysed specimens from 64 patients with primary breast cancer for their individual expression levels of several MDR-associated genes (MDR1, MRP, LRP (lung cancer resistance-related protein), topoisomerase (Topo) II alpha/IIbeta, cyclin A and the PKC isozyme genes (alpha, beta1, beta2, eta, theta, and mu) by a cDNA-PCR approach. We found significantly enhanced mean values for MRP, LRP and PKC eta gene expression, but significantly decreased Topo II alpha and cyclin A gene expression levels in G2 tumours compared with G3. Remarkably, significant positive correlations between the MDR1, MRP or LRP gene expression levels and PKC eta were determined: MDR1/PKC eta (rs = +0.6451, P < 0.0001) n = 62; MRP/PKC eta (rs = +0.5454, P < 0.0001) n = 63; LRP/PKC eta (rs = +0.5436, P < 0.0001) n = 62; MRP/LRP (rs = +0.7703, P < 0.0001) and n = 62, MDR1/MRP (rs = +0.5042, P < 0.0001) n = 62. Our findings point to the occurrence of a multifactorial MDR in the clinics and to PKC eta as a possible key regulatory factor for up-regulation of a series of MDR-associated genes in different types of tumours.
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DOI：
10.1006/bbrc.1995.1017
发表时间：
1995-01-05
影响因子：
3.1
作者：
GEKELER, V;BOER, R;BECK, J
通讯作者：
BECK, J
影响因子：
4.8
作者：
Germann, UA;Chambers, TC;Gottesman, MM
通讯作者：
Gottesman, MM
影响因子：
3.5
作者：
GRUNICKE, H;HOFMANN, J;UBERALL, F
通讯作者：
UBERALL, F
DOI：
10.1016/s0006-291x(05)80921-0
发表时间：
1990-12-31
影响因子：
3.1
作者：
SATO, W;YUSA, K;TSURUO, T
通讯作者：
TSURUO, T
影响因子：
8.8
作者：
BLOOM, H J;RICHARDSON, W W
通讯作者：
RICHARDSON, W W