Analysis of high fat diet induced genes during mammary gland development: identifying role players in poor prognosis of breast cancer

BMC Research Notes

Robert K Dearth²  Megan Keniry¹  Raquel C Martinez-Chacin¹ 

[1]Department of Biology, University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA

[2]Department of Biology, University of Texas-Pan American, 1201 West University Drive, Edinburg, Texas 78539-2999, USA

关键词: Diet-induced genes;    Mammary gland development;    Poor prognosis;    High fat diet;    Basal-like breast cancer;    Breast cancer;   

Others  :  1130355
DOI  :  10.1186/1756-0500-7-543

 received in 2014-02-25, accepted in 2014-08-07,  发布年份 2014

【 摘 要 】

Background

Epidemiological studies have shown that consumption of a high-fat diet (HFD) increases the risk of developing breast cancer (BC). Studies in rodents have shown HFD causes changes in the genetic programming of the maturing mammary gland (MG) increasing the susceptibility of developing the disease. Less is known about how HFD induced genes impact BC development. HFD exposure two weeks before conception to six weeks of age was previously shown to dramatically change MG gene expression in 10 week old mice. Therefore, we investigated these differentially expressed HFD-induced genes for their expression in BC using the NKI 295 breast tumor dataset.

Results

To examine the potential role of HFD induced genes in BC, we first investigated whether these HFD-induced genes in mouse MGs were differentially expressed in different types of human BC. Of the 28 HFD induced genes that were differentially expressed between BC subtypes in the NKI set, 79% were significantly higher in basal-like BC. Next, we analyzed whether HFD induced genes were associated with BC prognosis utilizing gene expression and survival data for each HFD induced gene from the NKI data and constructed Kaplan Meier survival plots. Significantly, 93% of the prognosis associated genes (13/14) were associated with poor prognosis (P = 0.002). Kaplan Meier analysis with 249 non-basal-like BC found that all but one of the genes examined were still significantly associated with poor prognosis. Furthermore, gene set enrichment analysis (GSEA) with HFD microarray data revealed that invasive BC genes where enriched in HFD samples that also had lost expression of luminal genes.

Conclusions

HFD exposed mouse MGs maintain differential expression of genes that are found highly expressed in basal-like breast cancer. These HFD-induced genes associate with poor survival in numerous BC subtypes, making them more likely to directly impact prognosis. Furthermore, HFD exposure leads to a loss in the expression of luminal genes and a gain in expression of mesenchymal and BC invasion genes in MGs. Collectively, our study suggests that HFD exposure during development induces genes associated with poor prognosis, thus identifying how HFD diet may regulate BC development.

【 授权许可】

   
2014 Martinez-Chacin et al.; licensee BioMed Central Ltd.

【 图 表 】

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