ANTIESTROGEN ACTION AND GROWTH-FACTOR REGULATION

The basis of the anti-proliferative action of antiestrogens is general ly considered to be their ability to inhibit estrogen induced growth p athways by competitively inhibiting the binding of estrogen to the est rogen receptor. Recent data suggest that this may not be the entire st ory. Moreover, the cascade of events responsible for inhibition of mit ogenesis after an initial interaction with the estrogen receptor is po orly understood. Multiple growth factor pathways operate in both norma l and neoplastic estrogen/antiestrogen target tissues. While it is unl ikely that any single pathway is pivotal, interactions of estrogen and /or antiestrogens with some of these pathways have been implicated in their proliferative effects. The exact molecular mechanisms remain unc lear but autocrine, paracrine/juxtacrine, intracrine, and endocrine me diators or various combinations of them are likely to be involved in v ivo. Super-imposed on this is the possibility that 'cross-talk' betwee n intracellular signaling pathways may also be involved. Elucidation o f such molecular mechanisms will be important with respect to design o f novel antiestrogenic/antimitogenic drugs and alternative treatment s trategies for both breast and uterine cancer.