Abstract

s / Maturitas 81 (2015) 126–143 133 results have been obtained from in vitro and in vivo studies concerning the role of estrogens and, especially progestins, in breast epithelial cell proliferation and in breast carcinogenesis. MPA has been found to trigger massive RANKL expression in mouse mammary gland predisposing the tissue to malignant changes and even onset of development of breast cancer. So far, there is little data available on the RANKL expression in human postmenopausal breast tissues (HBT). Aim: We studied the effects of E2, MPA, and some SERMs on explant cultures of normal, peritumoral and tumoral HBTs to evaluate their regulation of the progesterone/RANKL pathway. Methods: The non-malignant ormalignant HBTswere obtained from postmenopausal women undergoing breast surgeries. HBTs were cultured with or without E2, MPA and SERMs (ospemifene, raloxifene and tamoxifene) for 7 and 14 days. Further, cultured explants were studied for morphology, expression of markers for proliferation and apoptosis, expression of steroid hormone receptors and RANKL by immunohistochemistry, Western blots and qRT-PCR. Results: (1) E2, MPA and E2+MPA induce cell proliferation and RANKL induction in post-menopausal HBTs (2) RANKL induction is increased in tumoral HBTs (3) tamoxifen inhibited proliferation and RANKL expression. Conclusion: The results suggest that progesterone/RANKL axis has an important role in the response of HBTs to the steroids or drugs used in menopause. http://dx.doi.org/10.1016/j.maturitas.2015.02.104

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