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

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art_KATAYAMA_Gene_Expression_Profile_in_Response_to_Doxorubicin_Rapamycin_2012.PDF (1.3 MB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER ASSOC CANCER RESEARCH
Autores
LIMA, Leandro de Araujo
Citação
MOLECULAR CANCER THERAPEUTICS, v.11, n.2, p.464-474, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
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URI
https://observatorio.fm.usp.br/handle/OPI/1093
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPS
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - LIM/21
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - LIM/35