Regulatory network of mitomycin C action in human colon cancer cells.
Regulatory network of mitomycin C action in human colon cancer cells.
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DOI：
10.1111/j.1349-7006.1999.tb00785.x
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发表时间：
1999-05
期刊：
影响因子：
--
通讯作者：
Nishiyama M
中科院分区：
文献类型：
--
作者：
Suzuki K;Yamamoto W;Park JS;Hanaoka H;Okamoto R;Kirihara Y;Yorishima T;Okamura T;Kumazaki T;Nishiyama M
人类癌细胞中存在一个由丝裂霉素C （mitomycin C， MMC）的激活和失活通路组成的网络。用编码NAD(P)H：醌氧化还原酶（DT - diaphorase， DTD）的人NQO1 cDNA稳定转染COLO201结肠癌细胞，获得了DTD活性提高约57倍的克隆细胞系。Northern分析显示，NADPH：细胞色素P450还原酶（P450还原酶）基因在转染的col201 /NQO1中表达减少，与NQO1表达增加相关。细胞生化特征显示谷胱甘肽（GSH）含量显著增加，P450还原酶活性显著降低。作为这些协调调节的结果，与亲本细胞相比，COLO201/NQO1对MMC的敏感性没有增加。对包括转染物在内的5种人结肠癌细胞系中DTD、P450还原酶和谷胱甘肽S转移酶（GST）特异性抑制剂的抑制分析表明，DTD和P450还原酶分别在DTD活性足够高的细胞和边缘DTD活性的细胞中对MMC的激活起重要作用。相反，GST似乎参与了高水平GST活性细胞的MMC失活。这些结果表明，DTD、P450还原酶、GSH和GST可能根据其在细胞中的水平，以补偿或竞争的方式共同作用，决定细胞对MMC的敏感性。
A network composed of activation and inactivation pathways to regulate mitomycin C (MMC) action is suggested to exist in human cancer cells. COLO201 colon cancer cells were stably transfected with human NQO1 cDNA that encodes NAD(P)H: quinone oxidoreductase (DT‐diaphorase, DTD), and a clonal cell line with about 57‐fold elevated DTD activity was obtained. Northern analysis revealed that expression of the NADPH:cytochrome P450 reductase (P450 reductase) gene was decreased in the transfectant, COLO201/NQO1, associated with the increase of NQO1 expression. Biochemical characterization of the cells showed a significant increase of the glutathione (GSH) content concomitantly with the decrease of the P450 reductase activity. As a result of these coordinated modulations, sensitivity of COLO201/NQO1 to MMC was not increased as compared to the parent cells. Analyses of inhibition by specific inhibitors of DTD, P450 reductase and glutathione S‐transferase (GST) in 5 human colon cancer cell lines including the transfectant showed that DTD and P450 reductase play significant roles in MMC activation in cells with sufficiently high DTD activity and with marginal DTD activity, respectively. In contrast, GST appeared to participate in MMC inactivation in cells with a high level of GST activity. These results indicated that DTD, P450 reductase, GSH and GST may act together compensatively or competitively, depending on their levels in cells, to determine the cellular sensitivity to MMC.
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影响因子：
15.9
作者：
ODwyer, PJ;Szarka, CE;Clapper, ML
通讯作者：
Clapper, ML
DOI：
10.1016/0167-4889(92)90145-2
发表时间：
1992-11-17
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
SINGH, SV;XU, BH;MIAN, AM
通讯作者：
MIAN, AM
DOI：
10.1073/pnas.83.12.4538
发表时间：
1986-06-01
影响因子：
11.1
作者：
RONINSON, IB;CHIN, JE;PASTAN, I
通讯作者：
PASTAN, I
影响因子：
3.9
作者：
OLeary, KA;McQuiddy, P;Kasper, CB
通讯作者：
Kasper, CB
影响因子：
3.9
作者：
SHEPHARD, EA;PALMER, CNA;PHILLIPS, IR
通讯作者：
PHILLIPS, IR