Mechanisms of ovarian steroid hormones and antioestrogens in the development of carcinomas of the breast and endometrium

The ovarian steroid hormones (e.g., estrogen and progesterone) exert their many cellular and organ-specific effects via steroid-hormone receptors. Ste roid-hormon-dependent genes are stimulated by binding of the ligand-recepto r complex to the DNA binding site. Most steroid-hormone-receptors in the br east and endometrium are located in the cell nuclei. Additionally, non-geno mic effects are mediated by intracellular proteins. Cell activities such as proliferation, differentiation, division and apoptosis are regulated by pr oto-oncogenes, tumor suppressor genes and mutator genes. Normally various r egulatory mechanisms are in balance. Dysfunctions in regulatory mechanisms are key steps in the malignant transformation of cells in the breast or end ometrium. Thus, the effects of steroid homones or anti-estrogens such as ta moxifen or ralofixene can be obviated despite the presence of functional re ceptors.