Prepubertal physical activity up-regulates estrogen receptor β, BRCA1 and p53 mRNA expression in the rat mammary gland

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Physical activity during childhood has been proposed to reduce later breast cancer risk. We investigated plausible mechanisms mediating the protective effects on the mammary gland using rat as a model system. Female Sprague-Dawley rat pups were randomized to exercise, sham-exercise control (sham) and non-manipulated control groups. Treadmill training (20-25 m min-1, 15% grade, 30 min day-1, 5 days week-1) was started on postnatal day 14 and continued through day 32. Mammary glands were obtained at 32, 48 and 100 days and assessed for changes in morphology, and expression of estrogen receptor (ER) -α and ER-β protein by immunohistochemistry and ER-β, BRCA1 and p53 mRNA expression by real-time PCR. The results indicated that the glands of rats exposed to exercise during prepuberty contained fewer terminal end buds (p<0.06) and more alveolar buds and lobules than the sham group (p<0.001). Thus, prepubertal physical activity may reduce later breast cancer risk by inducing elimination of targets for malignant transformation by differentiation. We also found that ER-α protein levels were significantly reduced (p<0.003) and ER-β levels were increased (p<0.025) in the ductal and lobular mammary epithelial structures in 100-day-old exercised rats, when compared to the sham group. Further, ER-β (p<0.05), BRCA1 (p<0.002) and p53 (p<0.05) mRNA levels were significantly higher in the mammary glands of 100-day-old exercised than sham control rats. Prepubertal physical activity may therefore lead to a reduction in later susceptibility to breast cancer by up-regulating tumor suppressor genes that repair DNA damage.