Patientenkolloquium 2020
Das Universitätsklinikum Bonn möchte Sie auch 2020 wieder für das Patientenkolloquium "Uni-Medizin für Sie: Mitten im Leben" herzlich einladen ... weiterlesen

„Molekulare Charakterisierung UV-induzierter primärer und metastasierender Melanome in einem neuen genetischen Mausmodell“ Teilprojekt A9 im Verbundprojekt „Molekulare Mechanismen der Entstehung und Progression des malignen Melanoms“

Intense intermittent UV exposure, particularly during childhood, is a major risk factor for the development of melanoma. Currently, the mechanisms by which UV radiation, the major environmental etiologic agent, and host factors including the individual genetic constitution contribute to melanomagenesis are incompletely understood. Experiments in UV-sensitive genetically engineered mouse melanoma models demonstrate a pivotal role for deregulated growth factor signaling through Ras-dependant signaling pathways and impaired cell cycle control by the Ink4a/Arf tumor suppressor gene for melanocyte transformation. However, observations in different models including our own work in Hgf-Cdk4R24C mice suggest that progressive tumor growth requires additional genetic or epigenetic changes which affect the balance between differentiation, proliferation and migration of tumor cells. A detailed characterization of tumor cell lines established from primary Hgf-Cdk4R24C mouse melanomas in the previous funding period revealed that constitutive activation of NF-κB-dependant pro-inflammatory genes is associated with increased proliferative activity, invasive growth and metastatic spread. In this project we will now investigate the role of NF-κB signaling pathways in tumorigenic and metastasiogenic tumor cell subpopulations for tumor progression. Our Hgf-Cdk4R24C melanoma cell lines are ideally suited to elucidate how NF-κB transcriptional activation is regulated in vitro and to determine its impact on differentiation, proliferation, immune cell recruitment, invasive growth and metastatic spread in vivo. Finally, the relevance of our findings will be analyzed in the human system.