Speaker: Brigitte Hantusch, Medical university of Vienna, Austria
Host: Nikola Zlatkov, Department of Molecular Biology
About the lecture:
Prostate Cancer (PCa) is the leading cause of cancer incidence in men. At the same time, reliable markers for improved diagnostics and therapeutic decisions are lacking. Growth of PCa is highly dependent on androgens, and hormone ablation therapy is a cornerstone of current therapeutic approaches. However, many PCa patients succumb to androgen-independent tumor growth in castration-resistant prostate cancer (CRPC). Expression and activation of androgen receptor (AR) in these tumors is no longer dependent on androgen stimulation.
While the tumor-promoting role of androgens is well established, the role of thyroid hormones (THs), and lipid-soluble vitamins (vitamin A, vitamin D) is largely unresolved. These ligands exert their functions through specific nuclear receptors (NRs) which belong to a protein superfamily that form ligand-dependent homo- and heterodimers. The respective NRs - TRs, RARs and VDR - function as complexes together with the cognate dimerization partner retinoic X receptor (RXR) and nuclear coactivator (NcoA) or corepressor (NcoR) factors to bind to genomic DNA at specific motifs and regulate transcription.
Accumulating evidence indicates an additional growth stimulatory role of non-steroidal hormone NRs in PCa, which could play an essential role in the advanced or treatment-resistant PCa stage. Yet, their activities and interplay in PCa are unknown and warrant more investigation. A deeper understanding of the molecular details of the intersection of TH, lipid-soluble vitamin and steroid hormone NR action is vital to developing novel diagnostic/prognostic markers and identifying therapeutic targets in PCa.
This talk will focus on the role and crosstalk of NRs in PCa, with an emphasis on advanced and drug-resistant PCa entities. We analyze the abundance and cellular distribution of NRs and the genes they regulate, and study whether their effects are competetive or synergistic. We compare these findings with those in more aggressive PCa. Using PCa patient cohorts, we validate whether NR expression and top-regulated genes represent biomarkers or prognostic factors in PCa. NR-regulated gene patterns may have the potential to provide therapeutic targets that help to overcome treatment resistance. The findings may improve the treatment of patients not only with prostate cancer, but also with other hormone-dependent cancers.
Integrated Biomedical Science Seminars: is a broad, open seminar series in life science that is arranged jointly.