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Title: Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours      
dateReleased:
06-01-2014
description:
BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-51632
refinement:
raw
alternateIdentifiers:
51632
keywords:
functional genomics
dateModified:
06-09-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-45
name:
Affymetrix GeneChip Mouse Genome 430 2.0 [Mouse430_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-51632/E-GEOD-51632.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-51632/E-GEOD-51632.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51632
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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