Dual role of estrogens in endometrial cancer
Keywords:
aromatase, steroid sulfatase, catechol estrogens, estrogen quinones, estrogen metabolismAbstract
Increased local concentrations of estrogens are a well-known risk factor for endometrial cancer. Estrogens can act as mitogens via the estrogen receptors, and by forming oxidative metabolites they can act as cancer initiators. The role of estrogens differs with the stage of the disease. In pre-cancerous endometrium, estrogens are converted into estrogen quinones, which are potent carcinogens and can act as cancer initiators. Estrogen quinones can react with DNA and cause DNA depurination. They are also involved in the formation of reactive oxygen species, which can additionally damage DNA and other cellular macromolecules. In fully developed cancers, the role of estrogens is mainly to stimulate cell proliferation and to inhibit apoptosis, which also increases the occurrence of random errors in DNA replication. Estrogen actions are regulated at the receptor level as well as at the levels of the estrogen biosynthesizing and metabolizing enzymes. These latter represent potential targets for the development of new therapeutics, while the oxidative metabolites of estrogens can serve as biomarkers for diagnosis and monitoring of endometrial cancer.Downloads
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