The mammary gland is a complex organ whose growth and development are controlled by the interaction of a wide variety of hormones and growth factors. These same factors play fundamental roles in the etiology and progression of the cancerous state. The first event in the action of these hormones and growth factors is the interaction with specific cell associated receptors. The availability and activity of each class of receptor is regulated by the ligand which it recognizes as well as the general hormonal/growth factor milieu of the target cell. Our emphasis has been on the interactions of prolactin, thyroid hormone, and estrogens with recent work also examining how epidermal growth factor (EGF), and EGF-like growth factors are affected by the interplay of these three classical hormones. In addition we have explored the relationship of membrane associated antiestrogen binding sites to the lactogenic hormone receptor and the action of platelet derived growth factor (PDGF) on human breast cancer cell growth in culture. T47D cells have specific PDGF receptors and respond to its growth promoting signal by inducing phosphorylation of a 65Kd protein in the calelectrin family. Lobulo-alveolar development of the mammary gland requires the priming action of both estrogen and progesterone to induce EGF receptors and production of EGF-like growth factors. In concert with insulin, prolactin and glucocorticoids, EGF or alpha-TGF can promote full lobulo-alveolar development in vitro. This effect is inhibited by beta-TGF. The primed mammary gland is more sensitive to alpha-TGF than to EGF. Growth promotion of MCF-7 human breast cancer cells by prolactin can occur in the complete absence of estrogens. Prolactin induced growth of the estrogen receptor negative Nb2 rat lymphoma cell can be blocked by non-steroidal antiestrogens such as tamoxifen. This action is through the membranous antiestrogen binding site (AEBS) which may be intimately associated with the prolactin receptor. The antiprolactin action of tamoxifen, working through the AEBS, may have important clinical implications.
