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Title: Transcription profiling of mouse PyV-MT treated with conjugated linoleic acid reveals it suppresses FAS and promotes mammary tumorigenesis in mice      
dateReleased:
06-11-2008
description:
Overexpression of fatty acid synthase (FAS) has been reported in both malignant and premalignant breast lesions, and has been associated with poor outcome. FAS has gained interest as a metabolic target for the treatment of breast cancer based on evidence that blockade with the antifungal antibiotic, cerulenin or synthetic inhibitor C75 inhibits proliferation of breast cancer cells and delays tumor development. Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit FAS in bovine mammary adipose. Based on previously well-documented anti-tumor activity of CLA, we hypothesized that one mechanism of CLA’s anti-tumorigenic activity may be metabolic blockade of FAS. We fed virgin PyV-MT transgenic mice a diet supplemented with either 1% CLA, as mixed isomers, or control chow for four weeks. Tissue histology was determined by H&E staining. cDNA microarray and real-time quantitative PCR were performed to determine relative expression of lipogenic genes. Western blots were used to examine relative protein expression of FAS. Differences in protein densitometry were analyzed using Students 2-sided T-test. Probability was determined using the binomial sign test. Level of significance for all tests was 0.05. H&E staining revealed a shift towards advanced mammary lesions in the CLA-fed mice compared to control animals (24/26 vs. 11/26) (p for trend < 0.001). Microarray analysis revealed a >2-fold decrease in FAS in the CLA-fed group compared to controls, and was confirmed by quantitative RT-PCR (p < 0.001) and Western blot. The decrease in FAS mRNA expression was unexpectedly associated with more advanced disease (p for trend < 0.01). Conclusions: Dietary CLA suppressed fatty acid synthase in the mammary glands of the PyV-MT mouse while promoting mammary tumor progression. Experiment Overall Design: PyV-MT and wild type FVB mice were obtained from Jackson Laboratories (Bay Harbor, ME) and housed 2–4 per cage in micro insulator rooms. Mice were genotyped according to Jackson Laboratory protocols (). PyV-MT positive females were randomly selected at four weeks of age to receive either a control AIN93G chow (n=5) or 1% CLA-supplemented chow (n=6). . Food disappearance and animal weights were recorded weekly. Animals were palpated three times a week, and tumor area (length x width) was measured by caliper. Only palpable masses with an area >/= 0.5 cm2 were considered established growths. Animals were euthanized by CO2 inhalation. Eight-week-old animals were selected for tissue histology and analysis of mRNA and protein expression. Mammary gland sections were collected and processed to obtain mRNA or protein lysate, paraffin embedded for histology, or stored in liquid nitrogen until further processing.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-10193
refinement:
raw
alternateIdentifiers:
10193
dateSubmitted:
01-16-2008
keywords:
functional genomics
dateModified:
05-01-2014
creators:
Margaret Flowers
availability:
available
types:
gene expression
name:
Mus musculus
name:
unknown experiment type
ID:
A-AFFY-45
name:
Affymetrix GeneChip Mouse Genome 430 2.0 [Mouse430_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-10193/E-GEOD-10193.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-10193/E-GEOD-10193.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=GSE10193
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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