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Expressioin data from mouse colorectal cancer grown in healthy liver or fatty liver with or without antiangiogenic treatment

ABSTRACT: Cancers located adjacent to adipose tissues often show intrinsic and acquired resistance to antiangiogenic therapy. The resistance is developed potentially via tumor cell metabolic paradigm shift. We use microarrays to detail the gene expression upon tumor grown in the healthy or fatty liver with or without antiangiogenic treatment. Inflammatory profile, fatty acid oxidation-related genes, FFA transporter-related genes, and energy metabolism-related genes have been examined.

ORGANISM(S): Mus musculus

PROVIDER: GSE113508 | GEO | 2018/04/24

REPOSITORIES: GEO

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Project description:Maternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation (MAP) procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid (PA) and stearic acid (SA) reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of PA, oleic acid (OA), and SA at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.

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Expressioin data from mouse colorectal cancer grown in healthy liver or fatty liver with or without antiangiogenic treatment

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