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Melatonin (MEL), in vivo, prevents promotion and growth of mammary tumors in rodents, whereas in vitro inhibits breast cancer cell proliferation and invasiveness.Among the different mechanisms by which MEL may influence mammary cancer, we have focused our interest on its interaction with estrogen-signaling pathways.MEL could influence estrogenic actions: a) by down-regulating gonadal synthesis of steroids; b) by interacting with the estrogen receptors (ER), thus behaving as selective ER modulators (SERM); and c) by down-regulating the activity the enzymes involved in the synthesis of estrogens from androgens, behaving as selective estrogen enzyme modulators (SEEM).