Impact of the cellular estradiol response on the therapeutic inhibition of growth factor signaling

Abstract

Cellular response to estradiol stimuli ist mediated by different signal transduction cascades. In addition to classical mechanisms like the activation of estrogen response elements, there is increasing interest in the so-called non- nuclear actions of estrogens. It has been shown, that the estradiol-induced activation of cytoplasmic kinases is an important alternative mechanism of the cellular estradiol response. Consequently, the question has been raised, whether estradiol-induced activation of growth factor signaling would be able to interfere with the action of antitumoral substances directed against receptor-tyrosine kinase signal transduction. Recent data demonstrated, that estradiol is able to diminish the effects of antitumoral drugs targeting the HER2 receptor in vitro. Novel insights into the non-nuclear estradiol response and its impact on the efficacy of antitumoral drugs observed in endometrial tumor cells are reviewed.