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 antibodies. Loss of Fas/Apo-1 receptor leads in (lpr,lpr) mice to a nonmalignant accumulation of abnormal T-cells very probably due to the lack of induction of apoptosis in peripheral T-cells. It has been reported that soluble forms of Fas/Apo-1 receptor that may interfere with apoptotic signaling occur in patients suffering from various forms of lymphoid 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 Moloney Murine Leukemia Virus (MoMuLV) that causes T-cell lymphoma in mice and (ii) we crossed (lpr,lpr) animals with E mu L-myc transgenic mice that are prone to develop T- and B-cell lymphoma due to deregulated expression of the L-myc transgene by the immunoglobulin enhancer E mu. We find that infection with MoMuLV did not accelerate the formation of lymphoid neoplasms in (lpr,lpr) mice when compared to infected normal animals. However, E mu L-myc/(lpr,lpr) animals that constitutively express the L-myc transgene in the lymphoid lineage clearly show accelerated 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 indeed affect and modulate the process of tumor formation.
Zörnig
M
M
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps Universität Marburg, Germany.
Grzeschiczek
A
A
Kowalski
M B
MB
Hartmann
K U
KU
Möröy
T
T
D000818:Animals; D017209:Apoptosis; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D016259:Genes, myc; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000209:etiology* / Q000235:genetics / Q000821:virology; D016399:Lymphoma, T-Cell / Q000737:chemistry* / Q000209:etiology* / Q000235:genetics / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus; D011956:Receptors, Cell Surface / Q000502:physiology*; D012192:Retroviridae Infections; D014412:Tumor Virus Infections
D011956:Receptors, Cell Surface