Group Leaders: PD Dr. med. Andreas R. Günthert and Prof. Dr. rer. nat. Carsten Gründker
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About 50-64% of human breast cancers express receptors for GnRH. Direct antiproliferative effects of GnRH analogs on human breast cancer cell lines have been shown. They are at least in part mediated by antagonizing growth promoting effects of estradiol, epidermal growth factor (EGF) or insulin-like growth factor (IGF-1/-II). Pretreatment with GnRH analogs blocked EGF-induced autophosphorylation of EGF receptor and activation of mitogen-activated protein kinase (extracellular-signal-regulated kinase 1/2 (ERK1/2)) in these cells. In sublines of MCF-7 and T47D breast cancer cells, which were developed to be resistant to the anti-estrogen 4OH-tamoxifen, HER-2/p185 was overexpressed. Pretreatment of these cell lines with GnRH analogs completely abolished resistance to 4OH-tamoxifen, assessed by 4OH-tamoxifen-induced apoptosis. GnRH analogs counteract EGF-dependent signal transduction in GnRH receptor-positive human breast cancer cells. Through this mechanism, they probably reverse acquired resistance to 4OH-tamoxifen mediated through overexpression or activation of receptors of the c-erbB family.
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Funding:
Deutsche Forschungsgemeinschaft (GU 981/1-1), approved on 11/29/2005 for 2 Years.
Selected Publications: