Breast cancer

Functional characterization of molecular targets for breast cancer therapy

Breast cancer is the most frequent malignant tumor of women worldwide. Approximately 1 out of 10 women will eventually develop breast cancer over her lifetime. Understanding the pathways that promote breast cancer development and progression is crucial for an effective treatment of the disease. This project aims at the identification and functional characterization of novel factors linked to breast cancer etiology. Currently we are interested in determining the significance of the orphan nuclear receptor ERR alpha (Estrogen-Related Receptor alpha) as a possible alternative target for treatment resistant breast carcinomas.
ERR alpha displays high homology to the estrogen receptor alpha (ER alpha) although it does not bind natural estrogens. Both receptors are functional closely related and are discussed as controlling overlapping regulatory pathways. Expression status of ERR alpha in breast tumors correlates with an increased risk of cancer recurrence and a poor prognosis for patients. To decipher mechanisms of ERR alpha action we investigate the expression of ERR alpha, relevant cofactors, breast cancer markers and target genes in breast cancer tissue samples. We further define ERR alpha action by various functional assays in breast cancer cell lines employing shRNA mediated knock down or inactivation of ERR alpha by small molecule inhibitors. In particular we focus on the relationship between ERR alpha and ER with regard to regulation of shared target genes and on ERR alpha interplay with pathways associated with hormone resistant breast cancer. These studies will help to establish alternative treatment strategies for mammary carcinomas.



Collaborations
Prof. Dr. Andreas Schneeweiss, University Women's Hospital, Heidelberg