Global expression profiling of treatment-induced senescence in mouse Emu-myc B-cell lymphomas

Therapy-induced senescence (TIS) is a DNA damage-triggered irreversible cell-cycle block that terminates further expansion of (pre-)malignant lesions. Utilizing the Eµ-myc transgenic mouse lymphoma model (apoptosis protected by retroviral Bcl2-overexpression), we sought to elucidate the biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment. We used global gene expression profiling by microarrays to gain insight into the molecular program underlying the treatment-induced senescence in Emu-myc transgenic B-cell lymphomas (apoptosis protected by Bcl2 overexpression), which robustly enter senescence in response to DNA-damaging anticancer agents such as Adriamycin (ADR). We used primary lymphoma cells isolated from lymph nodes of Emu-Myc transgenic mice. In this model, the c-Myc oncogene is constitutively expressed in the cells of the B-cell lineage, leading to spontaneous development of aggressive B-cell lymphomas, resembling Burkitt lymphoma in humans. In order to bring up the senescence as the main fail-safe mechanism, primary lymphoma cells are protected from apoptosis by retroviral over-expression of Bcl2. These cells (Myc;Bcl2) massively undergo senescence upon DNA-damaging treatment. Adriamycin (ADR) is a cytostatic drug, used as a standard part of several lymphoma treatment regimens. In this study, transcriptional profiles of matched pairs of untreated vs. 5 days ADR-treated Myc;Bcl2 lymphomas were analysed.