Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380.
Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380.
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DOI：
10.18632/oncotarget.2814
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Fang B
中科院分区：
文献类型：
--
作者：
Huang X;Cao M;Wang L;Wu S;Liu X;Li H;Zhang H;Wang RY;Sun X;Wei C;Baggerly KA;Roth JA;Wang M;Swisher SG;Fang B
小分子抗癌剂NSC-743380调节多种癌症相关途径的功能，并且在NCI-60细胞系组中的癌细胞系亚组中具有高度活性。它还具有很好的体内抗癌活性。然而，NSC-743380的选择性抗癌活性的潜在机制仍未表征。为了确定可用于鉴定这种新型抗癌药物应答者的生物标志物，我们对NSC-743380的抗癌活性和NCI-60细胞系中的基因表达水平进行了相关性分析，并表征了NSC-743380介导的抗癌活性中最相关基因的功能。我们发现磺基转移酶SULT 1A 1与NSC-743380的抗癌活性有因果关系。SULT 1A 1在NSC-743380敏感细胞系中表达，但在耐药癌细胞中检测不到。NSC 743380抗性癌细胞中SULT 1A 1的异位表达显著地使抗性细胞对NSC-743380敏感。NSC-743380敏感性癌细胞系中SULT 1A 1的敲低使其对NSC-743380具有抗性。来自18个白血病细胞系的细胞裂解物中的SULT 1A 1蛋白水平可靠地预测了细胞系对NSC-743380的易感性。因此，SULT 1A 1在癌细胞中的表达是NSC-743380的抗癌活性所必需的，并且可以用作鉴定NSC-743380应答者的生物标志物。
The small molecule anticancer agent NSC-743380 modulates functions of multiple cancer-related pathways and is highly active in a subset of cancer cell lines in the NCI-60 cell line panel. It also has promising in vivo anticancer activity. However, the mechanisms underlying NSC-743380's selective anticancer activity remain uncharacterized. To determine biomarkers that may be used to identify responders to this novel anticancer agent, we performed correlation analysis on NSC-743380's anticancer activity and the gene expression levels in NCI-60 cell lines and characterized the functions of the top associated genes in NSC-743380–mediated anticancer activity. We found sulfotransferase SULT1A1 is causally associated with NSC-743380's anticancer activity. SULT1A1 was expressed in NSC-743380–sensitive cell lines but was undetectable in resistant cancer cells. Ectopic expression of SULT1A1 in NSC743380 resistant cancer cells dramatically sensitized the resistant cells to NSC-743380. Knockdown of the SULT1A1 in the NSC-743380 sensitive cancer cell line rendered it resistance to NSC-743380. The SULT1A1 protein levels in cell lysates from 18 leukemia cell lines reliably predicted the susceptibility of the cell lines to NSC-743380. Thus, expression of SULT1A1 in cancer cells is required for NSC-743380's anticancer activity and can be used as a biomarker for identification of NSC-743380 responders.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
--
作者：
Brunelli L;Caiola E;Marabese M;Broggini M;Pastorelli R
通讯作者：
Pastorelli R
影响因子：
45.3
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
通讯作者：
Slamon, DJ
影响因子：
64.5
作者：
Govindan R;Ding L;Griffith M;Subramanian J;Dees ND;Kanchi KL;Maher CA;Fulton R;Fulton L;Wallis J;Chen K;Walker J;McDonald S;Bose R;Ornitz D;Xiong D;You M;Dooling DJ;Watson M;Mardis ER;Wilson RK
通讯作者：
Wilson RK