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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
sihorike@staff.kanazawa-u.ac.jp
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| Phone |
+81-76-265-2775
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| Organization name |
Kanazawa University
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| Department |
Research Center for Experimental Modeling of Human Disease
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| Lab |
HORIKE Lab
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| Street address |
13-1 Takaramachi
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| City |
Kanazawa |
| State/province |
Ishikawa |
| ZIP/Postal code |
920-0934 |
| Country |
Japan |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA603377 |
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