The estrogen-induced pituitary tumor of the Fischer 344 (F344) rat has many important similarities to human breast cancer. These tumors occur in 100% of F344 rats treated with estrogen and are discernible by 3 weeks of treatment. Because of the existence of rat strains that are resistant to these tumors, we can use techniques of genetic analysis on this animal model to gain a better understanding of tumor growth. It is generally accepted that estrogens play a major role in the development of breast cancer in humans. Evidence supporting this hypothesis includes the correlation of lifetime estrogen exposure with breast cancer incidence, and the estrogen-dependence of breast cancer cells grown in vitro or when these cells are transplanted into animal models (Nandi et al., 1995). Despite a great deal of experimental and clinical data. estrogen's exact role in breast cancer is not understood. How and when estrogen promotes cancer and its molecular targets needs to be understood in order to design more effective treatments to cure this second-most lethal cancer in women. Such an endeavor is complicated by the fact that estrogen is also required for normal breast development. Thus, estrogen stimulus of mammary growth and development is normally limited by control mechanisms that fail to function in estrogen-dependent tumors. Such a balance of stimulation and control of growth can be seen in certain animal models. As shown in Figure 1, when estrogen is continuously administered to a variety of rat strains, DNA synthesis rate and cell proliferation increase in the uterus during a 24 to 48 hour period but then return to prestimulation levels despite the continued presence of estrogen (Wiklund and Gorski, 1982). In other words, a control mechanism exists to limit the extent of stimulation. The pituitary gland of most rat strains responds to estrogen similarly. However, in F344 rats, DNA synthesis remains elevated and growth proceeds continuously for at least 12 weeks of estrogen treatment. After 8 weeks of exposure to chronic high doses of estrogen, the pituitaries of F344 rats increase in mass 5-to