An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells.
BACKGROUND
The 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.


METHODS
Public 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.


RESULTS
In 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.


CONCLUSIONS
This 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.
Mandal
Soma
S
Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg Manitoba, R3E 0V9, Canada. mandals0@cc.umanitoba.ca
Davie
James R
JR
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*
D011960:Receptors, Estrogen; D004958:Estradiol