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Series GSE144328 Query DataSets for GSE144328
Status Public on May 24, 2020
Title Peri-pubertal High-Fat Diet Promotes c-Myc Stabilization in Mammary Gland Epithelium
Organism Mus musculus
Experiment type Expression profiling by array
Summary Dietary fat consumption during rapid mammary gland developing period such as peri-pubertal maturation or pregnancy increases the risk for breast cancer. However, the molecular mechanism underlying this observation is not well elucidated. To provide mechanistic insight, we examined gene expression profile in mouse mammary epithelial cells (MMECs) exposed to high-fat diet (HFD) or control diet (CD). Trp53-/- female mice were treated with experimental diets for 5 weeks during the peri-puberty period (3 to 8 weeks of age). This treatment induced insignificant difference in body weight between mice exposed to HFD and CD. Gene Set Enrichment Analysis (GSEA) predicted elevated expression of c-Myc target genes when exposed to HFD. Consistently, we detected marked elevation of c-Myc protein and prolongation of its half-life in MMECs exposed to HFD suggesting that HFD increased its stability. Additionally, we observed increased phosphorylation at c-MycS62 with concomitant increase in ERK phosphorylation. HFD rendered Trp53-/- MMECs more colonogenic and spherogenic, which was antagonized by a c-Myc inhibitor. Oleic acid the main fatty acid constituent of the HFD and TAK-875 an agonist for G protein-coupled receptor 40 (a receptor for oleic acid) as well enhanced c-Myc stabilization and MMECs proliferation. Collectively, these data suggest that HFD exerts its effect on MMECs through the stabilization of an oncoprotein, deciphering a novel mechanism whereby dietary fat promotes mammary carcinogenesis.
Overall design Comparison between mouse mammary glands isolated from 8-week-old female Trp-53 knockout mice that had been fed with HFD (high-fat diet) or CD (control diet) for five weeks. There are three biological replicates for each condition.
Contributor(s) Kulathunga N, Kohno S, Linn P, Nishimoto Y, Horike S, Muranaka H, Takahashi C
Citation(s) 32437590
Submission date Jan 27, 2020
Last update date Aug 23, 2020
Contact name Shin-ichi Horike
Phone +81-76-265-2775
Organization name Kanazawa University
Department Research Center for Experimental Modeling of Human Disease
Street address 13-1 Takaramachi
City Kanazawa
State/province Ishikawa
ZIP/Postal code 920-0934
Country Japan
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (6)
GSM4285930 HFD_rep1
GSM4285931 HFD_rep2
GSM4285932 HFD_rep3
BioProject PRJNA603377

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Supplementary file Size Download File type/resource
GSE144328_RAW.tar 12.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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