Prof. Dr. rer. nat. Doris Mayer

Glycogen synthase kinase-3 (green) is a major regulator of estrogen receptor (red) activity.

Hormones are important messenger substances produced in specialized tissues of the body which influence the majority of the processes in a cell and in the body. For example, hormones control metabolic pathways and regulate the reproduction cycle. Hormones also play a predominant role in the development of cancer, since they regulate the multiplication and differentiation of cells. If the complex interactions between hormones and the communication with the target cells are disturbed, this can lead to uncontrolled cell proliferation and tumour development. The aim of our work is to understand how hormones influence breast cancer development. The steroid hormone estradiol is one of the main risk factors involved in breast cancer development. This hormone binds to estrogen receptor, a specific receptor located mainly in the nucleus of the cell, which then acts as a transcription factor regulating the expression of genes related to cell proliferation. Only recently it became evident that other hormones and hormone-like growth factors, which do not bind to the estrogen receptor but activate receptors located in the plasma membrane of the cell, activate signalling mechanisms which interact with estrogen receptor function and modulate its activity. Modulation is achieved by phosphorylation of amino acids in the estrogen receptor by protein kinases. Our work focuses on the characterisation of protein kinase action related to estrogen receptor function.

Growth factor activated tyrosine kinase receptors and downstream signalling pathways interact with estrogen receptor function in breast cancer cells. Some protein kinases which transmit the growth factor signal and phosphorylate the estrogen receptor at specific amino acids have been identified and characterised. Most of them are components of the MAP kinase and phosphatidylinositol 3-kinase/Akt pathways. Other protein kinases are cell cycle kinases. Our aim is to identify and characterise novel protein kinases related to estrogen receptor function. Understanding the mechanism of interaction between tyrosine kinase receptor activated signalling pathways and estrogen receptor activation will permit to interfere with this process and inhibit breast cancer development and progression.