Expression data from senescence-inducible Suv39h1-ERT2 primary mouse Emu-myc B-cell lymphoma

Treatment-induced senescence (TIS) is a DNA damage-triggered stress-response program, resulting in terminal arrest of affected cells. TIS plays an important role in cancer therapy, as many tumor cells would undergo TIS instead of apoptosis when exposed to standard chemotherapy regimens. The contribution of TIS to overall disease outcome is, however, unclear. To address this, we use lymphoma cells with conditional expression of the senescence-essential factor Suv39h1 (regulatable by 4-hydroxi-tamoxifen). Only cells with active Suv39h1 would undergo TIS in response to chemotherapy. Suv39h1 inactivation during the chemo-treatment would prevent TIS induction, while inactivation in fully senescent cells would allow outgrowth from the TIS cell cycle arrest. Such post-senescent cells (PS) show very different biological behavior than the cells growing in senescence-incompetent setting - never senescent (NS). The molecular characteristics of each of these treatment conditions are analyzed here by assessing global transcriptome data. We used global gene expression profiling by microarrays to gain insight in the molecular programme underlying the chemotherapy response in primary Emu-myc transgenic B-cell lymphomas. Primary Eµ-myc lymphomas with genetic deletion of Suv39h1 were retrovirally transduced with a Suv39h1-ERT2 fusion protein, enabling 4-OH-tamoxifen inducible activation of Suv39h1 function. In addition, all cells were transduced with anti-apoptotic factor Bcl2 in order to prevent apoptosis and potentiate senescence as a main stress-response mechanism to DNA-damaging therapy. Three biological replicates were used and treated in vitro with chemo-drug Adriamycin (ADR), with or without Suv39h1 activation (i.e. with or without 4-OHT treatment). After 5 days, the cells were transferred in ADR/4-OHT-free medium and cultivated for another 14 days (outgrowth populations).