Der Einfluss von Östrogen auf die Ausbildung eines nukleären Aktinnetzwerks in Mammakarzinomzellen

As an essential component of the cytoskeleton in eukaryotic cells, actin filaments participate in various important cellular processes. Many of these relate to dynamic processes within cells (vesicle transport) as well as the motility of cells themselves (migration, adhesion). However, a much more far-reaching task of actin filaments is being discussed: Their possible contribution to the regulation of gene expression. So far, there are no conclusive explanations as to the exact nature of the dynamic process, which leads to the approach of silencers, promoters and enhancers, separated by thousands of base-pairs. It has been repeatedly described that actin filaments (F-actin) seem to play a significant role in this process. However, such evidence has not yet been provided with certainty, especially as it has long been assumed that only actin monomers (G-actin) are present in the cell nucleus. For some years, however, this fact has been refuted, actin filaments could be detected in the cell nucleus of various cell lines. Here again the question arose, how these actin filaments are involved in gene expression and what might influence this interaction. In the context of this work it was shown that the human breast cancer cell line MCF-7 known to possess estrogen receptors not only has nuclear actin filaments but that the amount of nuclear actin filaments forming after serum stimulation seems to be dependent on a previously applied concentration of estrogen. In this work, as a possible explanation for the increased formation of nuclear F-actin after estrogen pretreatment an estrogen concentration-dependent decreased expression of the protein cofilin was shown. Estrogen leads in the mentioned cell line via the estrogen receptor ERα known to proliferation, which could be confirmed in this work by various growth assays. It is also known that after estrogen binding to the ERα this becomes active as a transcription factor for various genes. These genes include, but are not limited to, BRCA1, FOXA1 or TP53. Genes exert diverse influences on cells. In this work, it was investigated to what extent nuclear actin filaments in interaction with estrogen are involved in the expression of known estrogen-responsive genes. Here, estrogen-pretreated MCF-7 cells were compared directly, one of which had a wild-type variant of actin, whereas the other expressed a dysfunctional actin variant (R62D actin, lack of actin polymerization). In summary of the preliminary results obtained, there was no simple cause-and-effect relationship between estrogen, nuclear F-actin, and certain genes. However, a variety of new questions regarding the probably extremely complex function of F-actin in the expression of different genes in human tumor cells, as well as their influence by steroid hormones as external factors opened up.