Dataset Information

Murine Mammary fat pad on high fat diet

ABSTRACT: Younger age and obesity increase the incidence and rates of metastasis of triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. The tissue microenvironment, specifically the extracellular matrix (ECM), is known to promote tumor invasion and metastasis. We sought to characterize the effect of both age and obesity on the ECM of mammary fat pads. We used a diet-induced obesity (DIO) model where 10-week-old female mice were fed a high-fat diet (HFD) for 16 weeks or a control chow diet (CD) where time points were every 4 weeks to monitor age and obesity HFD progression. We isolated the mammary fat pads to characterize the ECM at each time point. Utilizing proteomics, we found that the early stages of obesity were sufficient to induce distinct differences in the ECM composition of mammary fat pads that promote TNBC cell invasion. ECM proteins previously implicated in driving TNBC invasion Collagen IV and Collagen VI, were enriched with weight gain. Together these data implicate ECM changes in the primary tumor microenvironment as mechanisms by which age and obesity contribute to breast cancer progression.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Subcutaneous Adipose Tissue

DISEASE(S): Obesity

SUBMITTER: Sydney Conner

LAB HEAD: Madeleine Oudin

PROVIDER: PXD050250 | Pride | 2024-06-06

REPOSITORIES: Pride

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			Action	DRS
	994_SJC_15Plex_Fractions_Report.xlsx	Xlsx
	rs210916_994_SJC_15Plex_Fraction10_01.raw	Raw
	rs210916_994_SJC_15Plex_Fraction11_01.raw	Raw
	rs210916_994_SJC_15Plex_Fraction12_01.raw	Raw
	rs210916_994_SJC_15Plex_Fraction1_01.raw	Raw

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Project description:Background: Post-menopausal obesity is an established risk factor for breast cancer. Consumption of diets high in fat is known to be highly correlated with obesity. In this, we sought to evaluate the interaction(s) between high fat diet, weight gain and mammary carcinogenesis using an obese-resistant and obese-prone rat model with direct correlates to human disease. Methods: Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly. Results: The DMBA-treated OR rats on the 39% safflower diet had significantly greater incidence of ductal carcinoma-in-situ (DCIS) lesions and significantly greater DCIS multiplicity than DMBA-treated OR rats on the 10% safflower diet. These differences were not seen in the OP strain. Gene expression analysis of mammary ductal epithelium from OR rats on the high fat diet showed significant upregulation of proliferation-related genes compared to those consuming the low fat safflower diet. Again, these differences were not seen in the OP strain. Conclusion: Our findings indicate that consumption of high fat safflower diet enhances mammary carcinogenesis in an OR rat strain through increased proliferation of mammary epithelium at the time of exposure, but not in the OP rat strain. Thus, the diet-induced increase in sensitivity was strain-specific and independent of weight gain or obesity level. Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly.

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Murine Mammary fat pad on high fat diet

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