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dietary energy restriction, steroidogenesis, gene expression, breast epithelium, abdominal adipose tissue
Background: Weight gain and excessive adiposity are associated with an increased risk of breast cancer, especially in postmenopausal women with a high circulating level of testosterone. In this in silico study, the effect of the dietary energy restriction (DER) on the expression of a panel of genes coding for the main enzymes involved in androgens and estrogens production was investigated in breast epithelium and abdominal adipose tissue of healthy women with excessive adiposity and randomly allocated to DER for one menstrual cycle or asked to continue their usual diet.
Methods: Wilcoxon-Signed-Rank test was used to assess the difference between paired samples before and after DER in the breast epithelium or adipose tissue, and Spearman’s rank correlation was used to investigate the correlation between genes.
Results: In response to DER, the expression of HSD17B12, the gene encoding the enzyme that catalyzes the conversion of inactive estrone into bioactive estradiol, was significantly (P=0.0059) downregulated in breast epithelium and adipose tissue. Furthermore, the expression of HSD17B12 negatively correlated with that of the LRP1 gene (r= -0.91, P<0.0001), which codes for a multitasking protein recently proposed as a tumor suppressor in breast epithelium.
Conclusion: Present results showed that, in addition to the recognized systemic effects (reduction of the fatty mass and decrease of circulating biomarkers of breast cancer risk), DER could act locally by down-regulating the expression of some genes pivotally involved in the production of biologically active estrogens, thus contributing to prevent the estrogen-dependent initiation of breast cancer.
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