Mechanisms of normal and malignant breast epithelial growth regulation.

In this presentation we review information highlighting the multiple roles of both steroidal and polypeptide regulators of mammary epithelial cell growth with some additional emphasis on the work of our laboratory. The effects of both classes of hormones are complex and involve multiple interactions with epithelial components (malignant or normal) and the stromal compartment. Estrogens induce growth regulatory polypeptide growth factors which are responsible for many of the induced phenotypic effects in hormone-dependent breast cancer. Progression of hormone-dependent breast cancer to hormone independence probably involves multiple genetic mechanisms of oncogene activation, loss of the estrogen receptor, or loss of hormone responsivity of other gene products. Initial carcinogenesis and progression of mammary epithelium to cancer probably also requires both proliferative stimuli (estrogen, polypeptide growth factors) and genetic damage, leading to qualitatively different hormonal responses (hormone responsive cancer). New therapeutic strategies based on these biological considerations are emerging, including a variety of approaches which interfere at multiple points with ability of ligand to induce receptor signaling.