Role of membrane-bound estrogen receptors in Tamoxifen-resistant breast cancers

• Applicant: Professor Dr. Thomas Kalinski
• Subject Area: Pathology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261401354

Tamoxifen is the therapeutical standard in estrogenreceptor-positive breast cancer. During the therapy tamoxifen resistance develops in the majority of patients, which means tumor relapse. The causes of tamoxifen resistance are manifold. Membrane-bound estrogenreceptors may play an important role in this process. In addition to G-protein-coupled estrogenreceptor GPR30 this project deals with the role of the membrane-bound estrogenreceptor ERalpha36 in the development of tamoxifen resistance. The question whether ERalpha36 is appropriate as prognostic or predictive marker in breast cancers will be answered using a well-documented collective of more than 300 cases of breast cancer. Moreover molecular interactions (crosstalk) of ERalpha36 and other estrogenreceptors such as GPR30 in the development of tamoxifen resistance will be analyzed in an established cell culture model of tamoxifen resistant breast cancer cell line. Furthermore, the alterations in gene and microRNA expression will be analyzed during tamoxifen therapy to discover the molecular steps in tamoxifen resistance. Finally we check if not-membrane-permeable estrogen-bound toxins may present a therapeutic option in cancers with membrane-bound estrogenreceptors. In conclusion this project will contribute to the development of novel biomarkers and therapies for tamoxifen resistant breast cancer.

• DFG Programme: Research Grants