GnRH agonist Triptorelin reverts increased expression of the cofactors AIB1 and SRC-1 in breast cancer cells

Tamoxifen is a partial estrogen-receptor antagonist that is widely used for the treatment of estrogen-receptor positive breast tumors. Tamoxifen resistance developing after long term treatment is the major cause of treatment failure. Recently, we have shown, that exposure to 50Hz electromagnetic fields induces a tamoxifen resistance-like behavior in the breast cancer cell line MCF-7 (Girgert et al. 2005). The mechanism leading to the reproducible induction of tamoxifen resistance in breast cancer by electromagnetic fields was the subject of this study. It should be shown whether the emergence of tamoxifen resistance could be omited by the treatment of the breast cancer cells with GnRH analogs.

MCF-7 cells were exposed to 50Hz electromagnetic fields of a flux density of 1.2µT for 48 hours. In parallel culture plates the breast cancer cells were additionally treated with various concentrations of the GnRH agonist Triptorelin. For the exposure to electromagnetic fields special incubators were designed. Gene expression of the estrogen receptor cofactors AIB1 (amplified in breast cancer) and SRC-1 (steroid receptor coactivator 1) was determined by RT-PCR of RNA isolated from exposed and sham exposed cells.

Exposure to 1.2µT increased the expression of AIB1 strongest after 24 hours. The induction of SRC-1 expression occured only after 48 hours of exposure. Expression of the corepressor N-CoR decreased after 24 hours exposure to 1.2 microT and RNA for the corepressor SMRT decreased after 48 hours. The increase in expression of AIB1 and SRC-1 by electromagnetic fields was completely omited if 10–5 M of the GnRH agonist Triptorelin was present during the exposure of the cells to electromagnetic fields. 10–7 M Triptorelin partly reduced the effect of electromagnetic fields on the expression of AIB1 and SRC-1.

References: Girgert R, Schimming H, Körner W, Gründker C, Hanf V (2005) Induction of tamoxifen resistance in breast cancer cells by ELF electromagnetic fields. Biochem Biophys Res Commun 336:1144–1149