Since the cloning of the estrogen receptor α (ERα) and subsequent identification of a second distinct form of ER, termed ERβ, a large volume of research has begun to define the molecular mechanisms of ER action. However, although great progress has been made, ER action is still poorly understood. It is expected that a better understanding of ER action may lead to novel strategies and targets for breast cancer prevention and treatment. One of the early-realized functions of the ER was regulation of growth factor signaling, but the degree of interaction between these two mitogenic signaling pathways could not have been anticipated. Recent evidence suggests that the ER and the growth-factor-signaling pathways intersect and directly interact at every level of signal transduction. The resulting synergism between ER and growth factors has been documented both in normal breast development and, importantly, in breast cancer progression and antiestrogen resistance. In this review, we will highlight our current understanding of the molecular mechanisms of cross-talk between ER and growth-factor-signaling pathways.
Presented at the First International Conference on Recent Advances and Future Directions in Endocrine Therapy for Breast Cancer, June 21–23, 2001, Cambridge, MA. A. L.'s research is supported by a Susan G. Komen Foundation Award and NIH Grant P50CA-58183. X. C. is a recipient of a USAMRC postdoctoral fellowship award (DAMD 17-01-0133).