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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP TRAPE, Adriana Priscila FMUSP-HC
KATAYAMA, Maria Lucia Hirata FMUSP-HC
ROELA, Rosimeire Aparecida FMUSP-HC
LIMA, Leandro de Araujo
BRENTANI, Maria Mitzi FMUSP-HC 2012
dc.identifier.citation MOLECULAR CANCER THERAPEUTICS, v.11, n.2, p.464-474, 2012
dc.identifier.issn 1535-7163
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.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 LIM/21 LIM/24 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 TRAPE, Adriana Priscila:FM: KATAYAMA, Maria Lucia Hirata:FM:MDR ROELA, Rosimeire Aparecida:FM:MDR BRENTANI, Helena:FM:MPS RAVACCI, Graziela Rosa:FM: BRENTANI, Maria Mitzi:FM:MDR · LIMA, Leandro de Araujo:Hosp AC Camargo Fund Antonio Prudente, CIPE, Lab Bioinformat & Bioestat, Sao Paulo, Brazil 2-s2.0-84856830942 WOS:000300415300020 PHILADELPHIA USA
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dc.description.index MEDLINE
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