Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA110737 | ENA |
REPOSITORIES: ENA
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Project description:Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
2008-11-19 | GSE13553 | GEO
Project description:Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation. Virgin, four-week-old PyV-mT mice were administered a diet of a mixed-isomer CLA formulation (1% wt/wt) (N=6) or control AIN96G diet (N=5) for four weeks. Measurements of food disappearance, weights and palpations were recorded weekly. All animals were euthanized at eight weeks of age. Formalin-fixed, paraffin-embedded mammary gland tissue was used for H&E and trichrome staining and immunohistochemistry for Ki67. Tissue levels of CLA were measured by gas chromatography. Thoracic mammary glands were fixed in glacial acetic acid:ethanol and carmine stained. cDNA microarray was performed on RNA from 6 CLA-fed mice and 4 control mice using the Affymetrix 430 2.0 mouse genome chips.
2008-11-18 | E-GEOD-13553 | biostudies-arrayexpress
Project 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. Keywords: dietary intervention to compare mammary tumorigenesis between groups
2008-01-17 | GSE10193 | GEO
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Project description:Suppressed cytokine and chemokine transcriptional signatures in mammary stem/progenitor cells are associated with dietary protection against Wnt1-driven mammary tumorigenesis
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