This chapter discusses the estrogen regulation of protein synthesis and cell growth in human breast cancer. Estrogen regulation of protein synthesis and cell growth represents a balance among complex molecular and cellular interactions. Through the estrogen receptor, estrogen binds to nuclear DNA and modulates the transcription of specific genes. These gene products can influence intracellular events in the estrogen-sensitive cell directly, as is the case with enzymes that support DNA synthesis. Estrogen effects in the estrogen-sensitive cell can be indirect, mediated by autocrine growth stimulators such as transforming growth factor (TGF)-α which are produced in response to estrogen, or autocrine growth inhibitors such as TGF-β, whose production is inhibited by estrogen. These factors subsequently bind to cell surface receptors and influence a secondary wave of cellular events. Through paracrine-acting growth factors such as platelet-derived growth factor (PDGF), estrogen can influence the growth of breast cells in a different, indirect manner. Epithelial cells which produce PDGF in response to estrogen can stimulate the growth of surrounding stromal cells. Estrogen-regulated proteins such as plasminogen activator and collagenase act on the tissues surrounding the breast epithelium and influence the biological behavior important to growth, such as tumor invasion and metastasis.
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