In prof. C. Schmitt’s laboratory, molecular mechanisms of cell’s response on stress are studies. Stress-mediated responses are accompanied by the induction of apoptosis or cell aging that stops precancer state of the cell and afterwards kills (or isolates) the changed cell. However, when the cell undergoes oncogenic stimulation over a long period of time, it can overcome the barrier and irretrievably acquire oncogenic phenotype. In prof. C. Schmitt’s laboratory, mouse models of lymphoma and other tumors caused by known genetic disorders were created to study cell’s response on stress, which is induced by the anticancer therapy. On the basis of those models, antitumor role of Suv39h1 histone methylase was shown. Suv39h1 histone methylase inhibition in mice led to the development of the B-cell lymphoma directed by the constitutive expression of the embedded Ras proto-oncogene. Methylation of the H3R9 histone (it is a target for the Suv39h1 methylase) prevented formation of lymphomas and initiated the process of B-cell aging as protective mechanism against aging in the Suv39h1-deficient mice. It was also established that genetic disorders in the INK4a/ARF locus had modulatory role in sensitivity/resistance of different lymphoma types to anticancer therapy. Oncogenic signals activated stress response in normal cells. That stress response is a peculiar barrier on the way of cell transformation from the normal cell into the tumor one. So cell aging or apoptosis induced by antitumor therapy is a protective mechanism that prevents further expansion (metastasis) of tumor cells.
Place of employment — Max-Delbrück-Center for Molecular Medicine, Germany.
Contacts — Augustenburger Platz 1, 13353 Berlin, Germany +49 (30) 450–553 687 clemens.schmitt@charite.de .
Publications — Oncogene-induced senescence: putting the brakes on tumor development. Braig M, Schmitt CA. Cancer Res. 2006;66:2881–4.Cellular senescence and cancer treatment. Schmitt CA. Biochim Biophys Acta. 2007;1775:5–20.
