Global Transcriptional Changes Following Statin Treatment in Breast Cancer.
Clin Cancer Res
; 21(15): 3402-11, 2015 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-25840970
ABSTRACT
BACKGROUND:
Statins purportedly exert antitumoral effects, but the underlying mechanisms are currently not fully elucidated. The aim of this study was to explore potential statin-induced effects on global gene expression profiles in primary breast cancer. EXPERIMENTALDESIGN:
This window-of-opportunity phase II trial enrolled 50 newly diagnosed breast cancer patients prescribed atorvastatin (80 mg/day) for 2 weeks presurgically. Pre- and posttreatment tumor samples were analyzed using Significance Analysis of Microarrays (SAM) to identify differentially expressed genes. Similarly, SAM and gene ontology analyses were applied to gene expression data derived from atorvastatin-treated breast cancer cell lines (MCF7, BT474, SKBR3, and MDAMB231) comparing treated and untreated cells. The Systematic Motif Analysis Retrieval Tool (SMART) was used to identify enriched transcription factor-binding sites. Literature Vector Analysis (LitVAn) identified gene module functionality, and pathway analysis was performed using GeneGo Pathways Software (MetaCore; https//portal.genego.com/).RESULTS:
Comparative analysis of gene expression profiles in paired clinical samples revealed 407 significantly differentially expressed genes (FDR = 0); 32 upregulated and 375 downregulated genes. Restricted filtration (fold change ≥1.49) resulted in 21 upregulated and 46 downregulated genes. Significantly upregulated genes included DUSP1, RHOB1, GADD45B, and RGS1. Pooled results from gene ontology, LitVAn and SMART analyses identified statin-induced effects on the apoptotic and MAPK pathways among others. Comparative analyses of gene expression profiles in breast cancer cell lines showed significant upregulation of the mevalonate and proapoptotic pathways following atorvastatin treatment.CONCLUSIONS:
We report potential statin-induced changes in global tumor gene expression profiles, indicating MAPK pathway inhibition and proapoptotic events.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Quinasas de Proteína Quinasa Activadas por Mitógenos
/
Transcriptoma
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suecia