Interaction between cellular estradiol response and receptor tyrosine kinase signaling: Implications for breast cancer therapy

Growth of breast cancer cells is regulated by estrogens and growth factors. Cellular response to these stimuli is mediated by estrogen receptors and receptor tyrosine kinases. Originally both pathways were considered as independent signaling mechanisms. Now there is evidence for a broad cross-talk between these signal transduction pathways. The relationship between overexpression of HER-2/neu receptor tyrosine kinase and tamoxifen resistance is a possible example for the clinical relevance of this signaling cross-talk. Additionally, nongenomic effects of estrogens are able to interfere with the action of antitumoral substances directed against dysregulated receptor tyrosine kinases by activation of kinases downstream the receptor. Novel insights into the molecular mechanisms underlying the cross-talk between both signaling mechanisms and their impact on the efficacy of antitumoral substances directed against these pathways are reviewed.