A c-Jun N-terminal kinase inhibitor, JNK-IN-8, sensitizes triple negative breast cancer cells to lapatinib
Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor...
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| Published in | Oncotarget Vol. 8; no. 62; pp. 104894 - 104912 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Impact Journals LLC
01.12.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1949-2553 1949-2553 |
| DOI | 10.18632/oncotarget.20581 |
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| Abstract | Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect. The combination significantly increases survival of mice bearing xenografts of MDA-MB-231 human TNBC cells. Our studies demonstrate that lapatinib treatment increases c-Jun and JNK phosphorylation indicating a mechanism of resistance. Combined, these compounds significantly reduce transcriptional activity of Nuclear Factor kappa B, Activating Protein 1, and Nuclear factor erythroid 2-Related Factor 2. As master regulators of antioxidant response, their decreased activity induces a 10-fold increase in reactive oxygen species that is cytotoxic, and is rescued by addition of exogenous antioxidants. Over expression of p65 or Nrf2 also significantly rescues viability during JNK-IN-8 and lapatinib treatment. Further studies combining JNK-IN-8 and lapatinib may reveal a benefit for patients with TNBC, fulfilling a critical medical need. |
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| AbstractList | Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect. The combination significantly increases survival of mice bearing xenografts of MDA-MB-231 human TNBC cells. Our studies demonstrate that lapatinib treatment increases c-Jun and JNK phosphorylation indicating a mechanism of resistance. Combined, these compounds significantly reduce transcriptional activity of Nuclear Factor kappa B, Activating Protein 1, and Nuclear factor erythroid 2-Related Factor 2. As master regulators of antioxidant response, their decreased activity induces a 10-fold increase in reactive oxygen species that is cytotoxic, and is rescued by addition of exogenous antioxidants. Over expression of p65 or Nrf2 also significantly rescues viability during JNK-IN-8 and lapatinib treatment. Further studies combining JNK-IN-8 and lapatinib may reveal a benefit for patients with TNBC, fulfilling a critical medical need.Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect. The combination significantly increases survival of mice bearing xenografts of MDA-MB-231 human TNBC cells. Our studies demonstrate that lapatinib treatment increases c-Jun and JNK phosphorylation indicating a mechanism of resistance. Combined, these compounds significantly reduce transcriptional activity of Nuclear Factor kappa B, Activating Protein 1, and Nuclear factor erythroid 2-Related Factor 2. As master regulators of antioxidant response, their decreased activity induces a 10-fold increase in reactive oxygen species that is cytotoxic, and is rescued by addition of exogenous antioxidants. Over expression of p65 or Nrf2 also significantly rescues viability during JNK-IN-8 and lapatinib treatment. Further studies combining JNK-IN-8 and lapatinib may reveal a benefit for patients with TNBC, fulfilling a critical medical need. Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect. The combination significantly increases survival of mice bearing xenografts of MDA-MB-231 human TNBC cells. Our studies demonstrate that lapatinib treatment increases c-Jun and JNK phosphorylation indicating a mechanism of resistance. Combined, these compounds significantly reduce transcriptional activity of Nuclear Factor kappa B, Activating Protein 1, and Nuclear factor erythroid 2-Related Factor 2. As master regulators of antioxidant response, their decreased activity induces a 10-fold increase in reactive oxygen species that is cytotoxic, and is rescued by addition of exogenous antioxidants. Over expression of p65 or Nrf2 also significantly rescues viability during JNK-IN-8 and lapatinib treatment. Further studies combining JNK-IN-8 and lapatinib may reveal a benefit for patients with TNBC, fulfilling a critical medical need. |
| Author | Edupuganti, Ramakrishna Van Den Berg, Carla L. Van Ravenstein, Sabrina Ebelt, Nancy D. Kaoud, Tamer S. Dalby, Kevin N. |
| AuthorAffiliation | 1 Institute of Cellular & Molecular Biology, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA 2 Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA 3 Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA 4 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, El-Minia 61519, Egypt |
| AuthorAffiliation_xml | – name: 1 Institute of Cellular & Molecular Biology, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA – name: 2 Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA – name: 3 Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA – name: 4 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, El-Minia 61519, Egypt |
| Author_xml | – sequence: 1 givenname: Nancy D. surname: Ebelt fullname: Ebelt, Nancy D. organization: Institute of Cellular & Molecular Biology, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA, Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA – sequence: 2 givenname: Tamer S. surname: Kaoud fullname: Kaoud, Tamer S. organization: Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA, Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, El-Minia 61519, Egypt – sequence: 3 givenname: Ramakrishna surname: Edupuganti fullname: Edupuganti, Ramakrishna organization: Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA – sequence: 4 givenname: Sabrina surname: Van Ravenstein fullname: Van Ravenstein, Sabrina organization: Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA – sequence: 5 givenname: Kevin N. surname: Dalby fullname: Dalby, Kevin N. organization: Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA – sequence: 6 givenname: Carla L. surname: Van Den Berg fullname: Van Den Berg, Carla L. organization: Institute of Cellular & Molecular Biology, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA, Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX 78723, USA |
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| Cites_doi | 10.1016/j.bbamcr.2007.01.002 10.1158/1535-7163.mct-06-0514 10.1074/jbc.M109.094441 10.1124/mol.109.061424 10.1016/j.cbi.2013.12.005 10.1074/jbc.271.23.13422 10.1016/j.humpath.2009.08.018 10.1002/ijc.22187 10.1186/bcr2635 10.1186/1476-4598-11-41 10.1007/s10549-011-1568-1 10.1016/j.humpath.2006.01.022 10.1073/pnas.0932692100 10.1016/j.chembiol.2011.11.010 10.1073/pnas.0603509103 10.1074/jbc.R900010200 10.1074/jbc.M208704200 10.1126/science.1141478 10.1038/sj.onc.1206186 10.1002/(sici)1097-0215(20000320)89:2<177::aid-ijc13>3.0.co;2-0 10.1093/annonc/mdm601 10.1093/carcin/bgn271 10.1371/journal.pone.0010443 10.1016/S0021-9258(17)39966-0 10.1038/srep28217 10.1158/1078-0432.ccr-06-1109 10.1158/0008-5472.can-09-1947 10.1007/s12272-009-2002-7 10.1074/jbc.C500353200 10.1038/sj.cdd.4401865 10.1172/JCI45014 10.1016/S0014-2999(99)00357-X 10.1038/35021093 10.1158/0008-5472.can-08-4490 10.1152/ajplung.90487.2008 10.1038/nature05474 10.1128/MMBR.00025-06 10.1042/BJ20021535 10.1158/1055-9965.EPI-06-0806 10.1371/journal.pone.0006146 10.1007/s10549-008-0055-9 10.1089/104454999314999 10.1155/2015/294303 10.1158/1535-7163.MCT-09-1171 10.1523/JNEUROSCI.21-01-00018.2001 10.1093/emboj/cdg379 10.1074/jbc.M100103200 10.1158/1078-0432.ccr-04-0220 10.7150/jca.9696 10.1200/JCO.2005.08.326 10.1016/j.bbrc.2013.07.014 10.1073/pnas.191367098 10.1038/nm.3854 10.1038/sj.onc.1204385 10.1073/pnas.89.12.5321 10.4049/jimmunol.1003626 10.1523/JNEUROSCI.2111-04.2004 10.1128/mcb.01657-08 10.1158/0008-5472.can-05-1182 10.1177/1947601911400901 10.1016/j.redox.2015.07.008 10.1038/nrc2981 10.1186/1750-2187-5-8 10.18632/oncotarget.3787 10.1242/jcs.019455 10.1007/s13277-016-4873-9 10.1158/1541-7786.mcr-06-0263 10.1007/s10059-009-0050-y 10.1038/sj.onc.1204678 10.7150/jca.2.435 10.1016/j.mehy.2013.08.024 10.1080/15384047.2016.1210728 10.1242/jcs.00812 10.1200/JCO.2007.14.4147 10.15252/msb.20145877 10.1158/0008-5472.can-06-2401 10.1016/j.ccr.2006.08.015 10.1126/science.7824938 10.1093/annonc/mds279 10.1200/jco.2005.03.3845 10.1158/0008-5472.can-05-2853 |
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| Keywords | lapatinib antioxidant triple negative breast cancer JNK oxidative stress |
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| References | Tang (47) 2010; 4 Kuznetsov (76) 2016; 6 Daniel (81) 1996; 271 Pollack (48) 2009; 4 Xia (66) 2010; 77 Vanden Berghe (85) 2009; 29 Rojo (10) 2005; 23 Song (71) 2014; 209 Yarden (23) 2007; 1773 Park (70) 2007; 67 Schutte (75) 2006; 66 Gao (84) 2011; 186 Van Den Berg (25) 2003; 22 Schutte (74) 2007; 5 Schumacker (80) 2006; 10 Pietenpol (6) 2011; 121 Perou (5) 2010; 12 Moasser (14) 2007; 445 Davis (54) 1995; 267 Wainer (55) 2001; 21 Franzoso (61) 2006; 13 Devi (18) 2012; 132 Gutkind (58) 2005; 280 Janssen-Heininger (32) 2008; 121 Van Den Berg (50) 2010; 5 Chou (39) 2010; 70 Pickett (72) 2009; 284 Matese (4) 2001; 98 Nabo (79) 2013; 81 Blackwell (12) 2008; 19 Waldman (49) 1995; 55 Ueno (44) 2011; 2 Winer (11) 2009; 115 Berger (13) 2006; 66 Giles (82) 2009; 27 O'Connor (37) 2012; 11 Fortunato (21) 2016; 37 White (63) 1995; 269 Zhou (26) 2010; 41 Boerner (15) 2010; 5 Sorger (36) 2015; 11 Conley (73) 1977; 252 Kerppola (56) 2001; 20 Lønning (2) 2003; 100 Rogers (16) 2007; 316 Caldas (46) 2005; 23 Biswal (68) 2009; 296 Libermann (87) 2003; 63 Kim (41) 2009; 32 Kobe (22) 2006; 70 Van Den Berg (30) 2015; 6 Van Den Berg (29) 2011; 286 Wang (20) 2015; 2015 LoGrasso (34) 2012; 19 Bernuau (86) 2001; 20 Van Den Berg (24) 2011; 2 Dormond (53) 2013; 438 Cohen (35) 2003; 371 Bannai (67) 2002; 277 Hotamisligil (31) 2006; 103 Gonzalez-Angulo (52) 2014; 5 Yodoi (83) 2001; 276 van Diest (27) 2006; 37 Williams (3) 2000; 406 Nicholson (28) 2000; 89 Martin (40) 2005 Biswal (69) 2002; 62 Doihara (42) 2007; 120 Pusztai (8) 2008; 26 Zhang (19) 2016; 17 Mak (78) 2011; 11 Gown (9) 2004; 10 Cuadrado (64) 2004; 24 Gray (77) 1992; 89 Wong (33) 2009; 30 Ueno (43) 2007; 6 Duffy (45) 2012; 24 Nakano (62) 2003; 22 Mandich (1) 2007; 16 Lamas (60) 2015; 6 Slamon (38) 2010; 9 St Clair (65) 1999; 18 Perou (7) 2007; 13 Cantarini (17) 2015; 21 Inagami (57) 1999; 376 Gilmer (51) 2009; 69 Marshall (59) 2003; 116 |
| References_xml | – volume: 1773 start-page: 1161 year: 2007 ident: 23 article-title: Regulation of MAPKs by growth factors and receptor tyrosine kinases publication-title: Biochim Biophys Acta doi: 10.1016/j.bbamcr.2007.01.002 – volume: 6 start-page: 2168 year: 2007 ident: 43 article-title: Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.mct-06-0514 – volume: 286 start-page: 15287 year: 2011 ident: 29 article-title: c-Jun N-terminal kinase 2 (JNK2) enhances cell migration through epidermal growth factor substrate 8 (EPS8) publication-title: J Biol Chem doi: 10.1074/jbc.M109.094441 – volume: 77 start-page: 784 year: 2010 ident: 66 article-title: Inhibitor of kappaB kinase beta regulates redox homeostasis by controlling the constitutive levels of glutathione publication-title: Mol Pharmacol doi: 10.1124/mol.109.061424 – volume: 209 start-page: 56 year: 2014 ident: 71 article-title: Nrf2/ARE pathway activation, HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling publication-title: Chem Biol Interact doi: 10.1016/j.cbi.2013.12.005 – volume: 271 start-page: 13422 year: 1996 ident: 81 article-title: Role of oxidants and antioxidants in the induction of AP-1, NF-kappaB, and glutathione S-transferase gene expression publication-title: J Biol Chem doi: 10.1074/jbc.271.23.13422 – volume: 41 start-page: 401 year: 2010 ident: 26 article-title: Elevated expression of phosphorylated c-Jun NH2-terminal kinase in basal-like and “triple-negative” breast cancers publication-title: Hum Pathol doi: 10.1016/j.humpath.2009.08.018 – volume: 120 start-page: 181 year: 2007 ident: 42 article-title: Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231) publication-title: Int J Cancer doi: 10.1002/ijc.22187 – volume: 12 start-page: R68 year: 2010 ident: 5 article-title: Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer publication-title: Breast Cancer Res doi: 10.1186/bcr2635 – volume: 11 start-page: 41 year: 2012 ident: 37 article-title: Gene expression changes as markers of early lapatinib response in a panel of breast cancer cell lines publication-title: Mol Cancer doi: 10.1186/1476-4598-11-41 – volume: 132 start-page: 109 year: 2012 ident: 18 article-title: ErbB1/2 tyrosine kinase inhibitor mediates oxidative stress-induced apoptosis in inflammatory breast cancer cells publication-title: Breast Cancer Res Treat doi: 10.1007/s10549-011-1568-1 – volume: 37 start-page: 668 year: 2006 ident: 27 article-title: c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer publication-title: Hum Pathol doi: 10.1016/j.humpath.2006.01.022 – volume: 100 start-page: 8418 year: 2003 ident: 2 article-title: Repeated observation of breast tumor subtypes in independent gene expression data sets publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0932692100 – volume: 19 start-page: 140 year: 2012 ident: 34 article-title: Discovery of potent and selective covalent inhibitors of JNK publication-title: Chem Biol doi: 10.1016/j.chembiol.2011.11.010 – volume: 103 start-page: 10741 year: 2006 ident: 31 article-title: Functionalinteractions between JNK1 and JNK2 isoforms in obesity and insulin resistance publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0603509103 – volume: 284 start-page: 13291 year: 2009 ident: 72 article-title: The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress publication-title: J Biol Chem doi: 10.1074/jbc.R900010200 – volume: 277 start-page: 44765 year: 2002 ident: 67 article-title: Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression publication-title: J Biol Chem doi: 10.1074/jbc.M208704200 – volume: 4 start-page: 35 year: 2010 ident: 47 article-title: The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines publication-title: Breast Cancer (Auckl) – volume: 316 start-page: 1039 year: 2007 ident: 16 article-title: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling publication-title: Science doi: 10.1126/science.1141478 – volume: 22 start-page: 602 year: 2003 ident: 25 article-title: An inhibitory function for JNK in the regulation of IGF-I signaling in breast cancer publication-title: Oncogene doi: 10.1038/sj.onc.1206186 – volume: 89 start-page: 177 year: 2000 ident: 28 article-title: Biological and clinical associations of c-jun activation in human breast cancer publication-title: Int J Cancer doi: 10.1002/(sici)1097-0215(20000320)89:2<177::aid-ijc13>3.0.co;2-0 – volume: 19 start-page: 1068 year: 2008 ident: 12 article-title: A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer publication-title: Ann Oncol doi: 10.1093/annonc/mdm601 – volume: 30 start-page: 222 year: 2009 ident: 33 article-title: c-Jun N-terminal kinase (JNK1) upregulates XIAP-associated factor 1 (XAF1) through interferon regulatory factor 1 (IRF-1) in gastrointestinal cancer publication-title: Carcinogenesis doi: 10.1093/carcin/bgn271 – volume: 5 start-page: e10443 year: 2010 ident: 50 article-title: Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model publication-title: PLoS One doi: 10.1371/journal.pone.0010443 – volume: 252 start-page: 6367 year: 1977 ident: 73 article-title: Purification of thioredoxin, thioredoxin reductase, and glutathione reductase by affinity chromatography publication-title: J Biol Chem doi: 10.1016/S0021-9258(17)39966-0 – volume: 6 start-page: 28217 year: 2016 ident: 76 article-title: BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine publication-title: Sci Rep doi: 10.1038/srep28217 – volume: 13 start-page: 2329 year: 2007 ident: 7 article-title: The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes publication-title: Clin Cancer Res doi: 10.1158/1078-0432.ccr-06-1109 – volume: 70 start-page: 440 year: 2010 ident: 39 article-title: Drug combination studies and their synergy quantification using the Chou-Talalay method publication-title: Cancer Res doi: 10.1158/0008-5472.can-09-1947 – volume: 32 start-page: 1351 year: 2009 ident: 41 article-title: Gefitinib induces apoptosis and decreases telomerase activity in MDA-MB-231 human breast cancer cells publication-title: Arch Pharm Res doi: 10.1007/s12272-009-2002-7 – volume: 55 start-page: 5400 year: 1995 ident: 49 article-title: ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor heterogeneity in human breast cancer publication-title: Cancer Res – volume: 62 start-page: 5196 year: 2002 ident: 69 article-title: Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray publication-title: Cancer Res – volume: 280 start-page: 35081 year: 2005 ident: 58 article-title: Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1 publication-title: J Biol Chem doi: 10.1074/jbc.C500353200 – volume: 13 start-page: 712 year: 2006 ident: 61 article-title: The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease publication-title: Cell Death Differ doi: 10.1038/sj.cdd.4401865 – volume: 121 start-page: 2750 year: 2011 ident: 6 article-title: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies publication-title: J Clin Invest doi: 10.1172/JCI45014 – volume: 376 start-page: 203 year: 1999 ident: 57 article-title: Epidermal growth factor receptor is indispensable for c-Fos expression and protein synthesis by angiotensin II publication-title: Eur J Pharmacol doi: 10.1016/S0014-2999(99)00357-X – volume: 406 start-page: 747 year: 2000 ident: 3 article-title: Molecular portraits of human breast tumours publication-title: Nature doi: 10.1038/35021093 – volume: 69 start-page: 6871 year: 2009 ident: 51 article-title: Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL publication-title: Cancer Res doi: 10.1158/0008-5472.can-08-4490 – volume: 296 start-page: L565 year: 2009 ident: 68 article-title: Nrf2 increases survival and attenuates alveolar growth inhibition in neonatal mice exposed to hyperoxia publication-title: Am J Physiol Lung Cell Mol Physiol doi: 10.1152/ajplung.90487.2008 – volume: 445 start-page: 437 year: 2007 ident: 14 article-title: Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3 publication-title: Nature doi: 10.1038/nature05474 – volume: 70 start-page: 1061 year: 2006 ident: 22 article-title: Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases publication-title: Microbiol Mol Biol Rev doi: 10.1128/MMBR.00025-06 – volume: 371 start-page: 199 year: 2003 ident: 35 article-title: The specificities of protein kinase inhibitors: an update publication-title: Biochem J doi: 10.1042/BJ20021535 – volume: 16 start-page: 439 year: 2007 ident: 1 article-title: Differences in risk factors for breast cancer molecular subtypes in a population-based study publication-title: Cancer Epidemiol Biomarkers Prev doi: 10.1158/1055-9965.EPI-06-0806 – volume: 4 start-page: e6146 year: 2009 ident: 48 article-title: Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery publication-title: PLoS ONE doi: 10.1371/journal.pone.0006146 – volume: 115 start-page: 115 year: 2009 ident: 11 article-title: Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer publication-title: Breast Cancer Res Treat doi: 10.1007/s10549-008-0055-9 – volume: 18 start-page: 709 year: 1999 ident: 65 article-title: An Intronic NF-kappaB Element Is Essential for Induction of the Human Manganese Superoxide Dismutase Gene by Tumor Necrosis Factor-alpha and Interleukin-1beta publication-title: DNA Cell Biol doi: 10.1089/104454999314999 – volume: 2015 start-page: 12 year: 2015 ident: 20 article-title: Increased Oxidative Stress as a Selective Anticancer Therapy publication-title: Oxid Med Cell Longev doi: 10.1155/2015/294303 – volume: 9 start-page: 1489 year: 2010 ident: 38 article-title: Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-09-1171 – volume: 21 start-page: 18 year: 2001 ident: 55 article-title: Nerve growth factor, but not epidermal growth factor, increases Fra-2 expression and alters Fra-2/JunD binding to AP-1 and CREB binding elements in pheochromocytoma (PC12) cells publication-title: J Neurosci doi: 10.1523/JNEUROSCI.21-01-00018.2001 – volume: 22 start-page: 3898 year: 2003 ident: 62 article-title: NF‐κB inhibits TNF‐induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death publication-title: EMBO J doi: 10.1093/emboj/cdg379 – volume: 276 start-page: 18399 year: 2001 ident: 83 article-title: Hemin-induced activation of the thioredoxin gene by Nrf2. A differential regulation of the antioxidant responsive element by a switch of its binding factors publication-title: J Biol Chem doi: 10.1074/jbc.M100103200 – volume: 10 start-page: 5367 year: 2004 ident: 9 article-title: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma publication-title: Clin Cancer Res doi: 10.1158/1078-0432.ccr-04-0220 – volume: 63 start-page: 2206 year: 2003 ident: 87 article-title: Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer publication-title: Cancer Res – volume: 5 start-page: 745 year: 2014 ident: 52 article-title: cMET Activation and EGFR-Directed Therapy Resistance in Triple-Negative Breast Cancer publication-title: J Cancer doi: 10.7150/jca.9696 – volume: 23 start-page: 5323 year: 2005 ident: 10 article-title: Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2005.08.326 – volume: 438 start-page: 32 year: 2013 ident: 53 article-title: Reactivation of AKT signaling following treatment of cancer cells with PI3K inhibitors attenuates their antitumor effects publication-title: Biochem Biophys Res Commun doi: 10.1016/j.bbrc.2013.07.014 – volume: 98 start-page: 10869 year: 2001 ident: 4 article-title: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.191367098 – volume: 21 start-page: 560 year: 2015 ident: 17 article-title: Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M publication-title: Nat Med doi: 10.1038/nm.3854 – volume: 269 start-page: L588 year: 1995 ident: 63 article-title: Activation of NF-kappa B and elevation of MnSOD gene expression by thiol reducing agents in lung adenocarcinoma (A549) cells publication-title: Am J Physiol – volume: 20 start-page: 2438 year: 2001 ident: 56 article-title: Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity publication-title: Oncogene doi: 10.1038/sj.onc.1204385 – volume: 89 start-page: 5321 year: 1992 ident: 77 article-title: ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.89.12.5321 – volume: 186 start-page: 3173 year: 2011 ident: 84 article-title: NF-kappaB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages publication-title: J Immunol doi: 10.4049/jimmunol.1003626 – volume: 24 start-page: 7324 year: 2004 ident: 64 article-title: Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-kappaB publication-title: J Neurosci doi: 10.1523/JNEUROSCI.2111-04.2004 – volume: 29 start-page: 5488 year: 2009 ident: 85 article-title: Hyperactivated NF-{kappa}B and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells publication-title: Mol Cell Biol doi: 10.1128/mcb.01657-08 – volume: 66 start-page: 1630 year: 2006 ident: 13 article-title: Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells publication-title: Cancer Res doi: 10.1158/0008-5472.can-05-1182 – volume: 2 start-page: 31 year: 2011 ident: 24 article-title: c-Jun N-terminal Kinase 2 Regulates Multiple Receptor Tyrosine Kinase Pathways in Mouse Mammary Tumor Growth and Metastasis publication-title: Genes Cancer doi: 10.1177/1947601911400901 – volume-title: ComboSyn, Inc year: 2005 ident: 40 – volume: 6 start-page: 183 year: 2015 ident: 60 article-title: Antioxidant responses and cellular adjustments to oxidative stress publication-title: Redox Biology doi: 10.1016/j.redox.2015.07.008 – volume: 11 start-page: 85 year: 2011 ident: 78 article-title: Regulation of cancer cell metabolism publication-title: Nat Rev Cancer doi: 10.1038/nrc2981 – volume: 5 start-page: 8 year: 2010 ident: 15 article-title: EGFR/Met association regulates EGFR TKI resistance in breast cancer publication-title: J Mol Signal doi: 10.1186/1750-2187-5-8 – volume: 6 start-page: 11863 year: 2015 ident: 30 article-title: c-Jun N-terminal kinase 2 prevents luminal cell commitment in normal mammary glands and tumors by inhibiting p53/Notch1 and breast cancer gene 1 expression publication-title: Oncotarget doi: 10.18632/oncotarget.3787 – volume: 121 start-page: 1036 year: 2008 ident: 32 article-title: Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1 publication-title: J Cell Sci doi: 10.1242/jcs.019455 – volume: 37 start-page: 4281 year: 2016 ident: 21 article-title: The role of oxidative stress on breast cancer development and therapy publication-title: Tumour Biol doi: 10.1007/s13277-016-4873-9 – volume: 5 start-page: 195 year: 2007 ident: 74 article-title: Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines publication-title: Mol Cancer Res doi: 10.1158/1541-7786.mcr-06-0263 – volume: 27 start-page: 279 year: 2009 ident: 82 article-title: Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin publication-title: Mol Cells doi: 10.1007/s10059-009-0050-y – volume: 20 start-page: 5132 year: 2001 ident: 86 article-title: Functional cooperation between JunD and NF-kappaB in rat hepatocytes publication-title: Oncogene doi: 10.1038/sj.onc.1204678 – volume: 2 start-page: 435 year: 2011 ident: 44 article-title: Gemcitabine Overcomes Erlotinib Resistance in EGFR-Overexpressing Cancer Cells through Downregulation of Akt publication-title: J Cancer doi: 10.7150/jca.2.435 – volume: 81 start-page: 866 year: 2013 ident: 79 article-title: Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (Anticancer effects of 3-bromopyruvate through antagonizing Warburg effect) publication-title: Med Hypotheses doi: 10.1016/j.mehy.2013.08.024 – volume: 17 start-page: 925 year: 2016 ident: 19 article-title: Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS publication-title: Cancer Biol Ther doi: 10.1080/15384047.2016.1210728 – volume: 116 start-page: 4957 year: 2003 ident: 59 article-title: Elevated ERK-MAP kinase activity protects the FOS family member FRA-1 against proteasomal degradation in colon carcinoma cells publication-title: J Cell Sc doi: 10.1242/jcs.00812 – volume: 26 start-page: 1275 year: 2008 ident: 8 article-title: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2007.14.4147 – volume: 11 start-page: 0797 year: 2015 ident: 36 article-title: Systematic analysis of BRAF(V)(600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis publication-title: Mol Syst Biol doi: 10.15252/msb.20145877 – volume: 67 start-page: 546 year: 2007 ident: 70 article-title: Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology publication-title: Cancer Res doi: 10.1158/0008-5472.can-06-2401 – volume: 10 start-page: 175 year: 2006 ident: 80 article-title: Reactive oxygen species in cancer cells: Live by the sword, die by the sword publication-title: Cancer Cell doi: 10.1016/j.ccr.2006.08.015 – volume: 267 start-page: 389 year: 1995 ident: 54 article-title: Transcription factor ATF2 regulation by the JNK signal transduction pathway publication-title: Science doi: 10.1126/science.7824938 – volume: 24 start-page: 362 year: 2012 ident: 45 article-title: ADAM-17: a novel therapeutic target for triple negative breast cancer publication-title: Ann Oncol doi: 10.1093/annonc/mds279 – volume: 23 start-page: 7350 year: 2005 ident: 46 article-title: Molecular classification and molecular forecasting of breast cancer: ready for clinical application? publication-title: J Clin Oncol doi: 10.1200/jco.2005.03.3845 – volume: 66 start-page: 41 year: 2006 ident: 75 article-title: BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants publication-title: Cancer Res doi: 10.1158/0008-5472.can-05-2853 |
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