An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cellsReport as inadecuate

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BMC Cancer

, 7:181

First Online: 20 September 2007Received: 06 February 2007Accepted: 20 September 2007DOI: 10.1186-1471-2407-7-181

Cite this article as: Mandal, S. & Davie, J.R. BMC Cancer 2007 7: 181. doi:10.1186-1471-2407-7-181


BackgroundThe sex hormone estrogen E2 is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER+ve breast cancer cells during E2 deprivation.

MethodsPublic repositories of SAGE and MA gene expression data generated from E2 deprived ER+ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology GO, enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status.

ResultsIn all GO terms, biological process BP, molecular function MF, and cellular component CC, MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein ZR75-1 and glucose metabolism MCF-7. A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization electron transport, proteasome, glycolysis-gluconeogenesis and expression ribosome in both cells, there was an overall similarity of ZR75-1 with ER-ve cell lines and ER+ve-ER-ve breast tumors.

ConclusionThis study demonstrates integral metabolic differences may exist within the same cell subtype luminal A in representative ER+ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER+ve breast tumors.

AbbreviationsSAGEserial analysis of gene expression

MicroarrayAffymetrix GeneChip MA

GenMAPPGene MA Pathway Profiler

DAVIDDatabase for Annotation, visualization, and integrated Discovery

GSEAgene set enrichment analysis.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-7-181 contains supplementary material, which is available to authorized users.

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Author: Soma Mandal - James R Davie


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