Gene Expression Profile in Response to Doxorubicin-Rapamycin Combined Treatment of HER-2-Overexpressing Human Mammary Epithelial Cell Lines

Show simple item record

dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author TRAPE, Adriana Priscila FMUSP-HC
KATAYAMA, Maria Lucia Hirata FMUSP-HC
ROELA, Rosimeire Aparecida FMUSP-HC
BRENTANI, Helena FMUSP-HC
RAVACCI, Graziela Rosa FMUSP-HC
LIMA, Leandro de Araujo
BRENTANI, Maria Mitzi FMUSP-HC
dc.date.issued 2012
dc.identifier.citation MOLECULAR CANCER THERAPEUTICS, v.11, n.2, p.464-474, 2012
dc.identifier.issn 1535-7163
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/1093
dc.description.abstract HER-2-positive breast cancers frequently sustain elevated AKT/mTOR signaling, which has been associated with resistance to doxorubicin treatment. Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification. The epithelial mammary cell line HB4a was also analyzed. The combined treatment using 20 nmol/L of rapamycin and 30 nmol/L of doxorubicin arrested HB4a and C5.2 cells in S to G(2)-M, whereas SKBR3 cells showed an increase in the G(0)-G(1) phase. Rapamycin increased the sensitivity to doxorubicin in HER-2-overexpressing cells by approximately 2-fold, suggesting that the combination displayed a more effective antiproliferative action. Gene expression profiling showed that these results might reflect alterations in genes involved in canonical pathways related to purine metabolism, oxidative phosphorylation, protein ubiquitination, and mitochondrial dysfunction. A set of 122 genes modulated by the combined treatment and specifically related to HER-2 overexpression was determined by finding genes commonly regulated in both C5.2 and SKBR3 that were not affected in HB4a cells. Network analysis of this particular set showed a smaller subgroup of genes in which coexpression pattern in HB4a cells was disrupted in C5.2 and SKBR3. Altogether, our data showed a subset of genes that might be more robust than individual markers in predicting the response of HER-2-overexpressing breast cancers to doxorubicin and rapamycin combination.
dc.description.sponsorship · FAPESP
· CnPq
dc.language.iso eng
dc.publisher AMER ASSOC CANCER RESEARCH
dc.relation.ispartof Molecular Cancer Therapeutics
dc.rights restrictedAccess
dc.subject.other breast-cancer cells; topoisomerase-ii-alpha; mammalian target; her2 status; mtor; chemotherapy; sensitivity; therapy; inhibitor; pharmacokinetics
dc.title Gene Expression Profile in Response to Doxorubicin-Rapamycin Combined Treatment of HER-2-Overexpressing Human Mammary Epithelial Cell Lines
dc.type article
dc.rights.holder Copyright AMER ASSOC CANCER RESEARCH
dc.description.group LIM/21
dc.description.group LIM/24
dc.description.group LIM/35
dc.identifier.doi 10.1158/1535-7163.MCT-11-0033
dc.identifier.pmid 22084168
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author TRAPE, Adriana Priscila:FM:
hcfmusp.author KATAYAMA, Maria Lucia Hirata:FM:MDR
hcfmusp.author ROELA, Rosimeire Aparecida:FM:MDR
hcfmusp.author BRENTANI, Helena:FM:MPS
hcfmusp.author RAVACCI, Graziela Rosa:FM:
hcfmusp.author BRENTANI, Maria Mitzi:FM:MDR
hcfmusp.author.external · LIMA, Leandro de Araujo:Hosp AC Camargo Fund Antonio Prudente, CIPE, Lab Bioinformat & Bioestat, Sao Paulo, Brazil
hcfmusp.origem.id 2-s2.0-84856830942
hcfmusp.origem.id WOS:000300415300020
hcfmusp.publisher.city PHILADELPHIA
hcfmusp.publisher.country USA
hcfmusp.relation.reference · Arpino G, 2005, BREAST CANCER RES TR, V92, P69, DOI 10.1007/s10549-005-1721-9
· BENJAMIN RS, 1977, CANCER RES, V37, P1416
· BERRIDGE MJ, 1989, CELL, V59, P411, DOI 10.1016/0092-8674(89)90026-3
· Carraro DM, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0021022
· Chan S, 2005, J CLIN ONCOL, V23, P5314, DOI 10.1200/JCO.2005.66.130
· Chuang HY, 2007, MOL SYST BIOL, V3, DOI 10.1038/msb4100180
· DiGiovanna MP, 2008, J CLIN ONCOL, V26, P2364, DOI 10.1200/JCO.2007.13.6580
· Dressler LG, 2005, J CLIN ONCOL, V23, P4287, DOI 10.1200/JCO.2005.11.012
· Gennari A, 2008, J NATL CANCER I, V100, P14, DOI 10.1093/jnci/djm252
· Glynn RW, 2010, ANN SURG ONCOL, V17, P1392, DOI 10.1245/s10434-009-0855-0
· Goldhirsch A, 2009, ANN ONCOL, V20, P1319, DOI 10.1093/annonc/mdp322
· Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008
· Harris RA, 1999, INT J CANCER, V80, P477, DOI 10.1002/(SICI)1097-0215(19990129)80:3<477::AID-IJC23>3.0.CO;2-W
· Hernandez-Aya LF, 2011, ONCOLOGIST, V16, P404, DOI 10.1634/theoncologist.2010-0402
· Hui STY, 2008, P NATL ACAD SCI USA, V105, P3921, DOI 10.1073/pnas.0800293105
· Jarvinen TAH, 2000, AM J PATHOL, V156, P839, DOI 10.1016/S0002-9440(10)64952-8
· Prasad TSK, 2009, NUCLEIC ACIDS RES, V37, pD767, DOI 10.1093/nar/gkn892
· KU DH, 1991, CELL GROWTH DIFFER, V2, P179
· Li XQ, 2005, BREAST CANCER RES, V7, pR589, DOI 10.1186/bcr1259
· Meric-Bernstam F, 2009, J CLIN ONCOL, V27, P2278, DOI 10.1200/JCO.2008.20.0766
· Miller TW, 2009, CLIN CANCER RES, V15, P7266, DOI 10.1158/1078-0432.CCR-09-1665
· Mondesire WH, 2004, CLIN CANCER RES, V10, P7031, DOI 10.1158/1078-0432.CCR-04-0361
· Morrow PK, 2011, J CLIN ONCOL, V10, P3126
· Mueller P, 2008, NAT IMMUNOL, V9, P424, DOI 10.1038/ni1570
· Noh WC, 2004, CLIN CANCER RES, V10, P1013, DOI 10.1158/1078-0432.CCR-03-0043
· Oakman C, 2009, CANCER TREAT REV, V35, P662, DOI 10.1016/j.ctrv.2009.08.006
· O'Reilly KE, 2006, CANCER RES, V66, P1500, DOI 10.1158/0008-5472.CAN-05-2925
· Possemato R, 2011, NATURE, V476, P346, DOI 10.1038/nature10350
· Pritchard KI, 2006, NEW ENGL J MED, V354, P2103, DOI 10.1056/NEJMoa054504
· R Development Core Team, 2009, R LANG ENV STAT COMP
· Rantala JK, 2010, NEOPLASIA, V12, P877, DOI 10.1593/neo.10548
· Raymond E, 2004, J CLIN ONCOL, V22, P2336, DOI 10.1200/JCO.2004.08.116
· Rody A, 2007, BREAST, V16, P86, DOI 10.1016/j.breast.2006.06.008
· Rulten SL, 2006, MAMM GENOME, V17, P322, DOI 10.1007/s00335-005-0127-7
· Schieke SM, 2008, J BIOL CHEM, V283, P28506, DOI 10.1074/jbc.M802763200
· Schieke SM, 2006, BIOL CHEM, V387, P1357, DOI 10.1515/BC.2006.170
· Schmidt O, 2010, NAT REV MOL CELL BIO, V11, P655, DOI 10.1038/nrm2959
· Slamon DJ, 2001, NEW ENGL J MED, V344, P783, DOI 10.1056/NEJM200103153441101
· Sokolosky ML, 2011, ONCOTARGET, V2, P538
· Steelman LS, 2008, ONCOGENE, V27, P4086, DOI 10.1038/onc.2008.49
· Taylor IW, 2009, NAT BIOTECHNOL, V27, P199, DOI 10.1038/nbt.1522
· Timms JF, 2002, ONCOGENE, V21, P6573, DOI 10.1038/sj.onc.1205847
· Vargas-Roig LM, 1998, INT J CANCER, V2, P129
· Wang YA, 2008, INT J CANCER, V123, P1536, DOI 10.1002/ijc.23671
· Wendel HG, 2006, CANCER RES, V66, P7639, DOI 10.1158/0008-5472.CAN-06-0419
dc.description.index MEDLINE
hcfmusp.citation.scopus 4
hcfmusp.citation.wos 5
hcfmusp.affiliation.country Brasil


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace



Browse

My Account

Statistics