LOSS OF FAS APO-1 RECEPTOR ACCELERATES LYMPHOMAGENESIS IN E-MU L-MYC TRANSGENIC MICE BUT NOT IN ANIMALS INFECTED WITH MOMULV/

The Fas/Apo-1 receptor is an integral membrane protein that transduces apoptotic signals upon binding to its natural ligand or to specific a ntibodies. Loss of Fas/Apo-1 receptor leads in (lpr;lpr) mice to a non malignant accumulation of abnormal T-cells very probably due to the la ck of induction of apoptosis in peripheral T-cells. It has been report ed that soluble forms of Fas/Apo-1 receptor that may interfere with ap optotic signaling occur in patients suffering from various forms of ly mphoid neoplasms. Therefore, we wished to investigate whether the loss of proper homeostatic regulation through Fas/Apo-1 receptor mediated apoptosis could influence the process of lymphomagenesis, To this end, we performed two experiments (i) we infected (lpr,lpr) animals with M oloney Murine Leukemia Virus (MoMuLV) that causes T-cell lymphoma in m ice and (ii) we crossed (lpr,lpr) animals with E mu L-myc transgenic m ice that are prone to develop T- and B-cell lymphoma due to deregulate d expression of the L-myc transgene by the immunoglobulin enhancer E m u. We find that infection with MoMuLV did not accelerate the formation of lymphoid neoplasms in (lpr,lpr) mice when compared to infected nor mal animals. However, E mu L-myc/(lpr,lpr) animals that constitutively express the L-myc transgene in the lymphoid lineage clearly show acce lerated formation of T- and B-cell lymphoma when compared to normal E mu L-myc transgenics. These data demonstrate that in cooperation with particular oncogenes impairment of Fas/Apo-1 receptor function can ind eed affect and modulate the process of tumor formation.