Perforin-mediated suppression of B-cell lymphoma.
In the present study, we have examined the effect of perforin (pfp) deficiency in 4 models of mouse B-cell lymphomagenesis. We have examined pfp loss on the background of either Mlh1 tumor suppressor allele loss or oncogene expression [Ig heavy chain (Emu)-v-Abl, Emu-myc, and vav-bcl2]. Pfp was shown to act as a suppressor of B-cell malignancies characteristically driven by v-Abl or bcl-2, whereas Mlh loss cooperated in accelerating spontaneous B-cell lymphomas characteristic of pfp loss. No protective role for pfp was observed in the more aggressive Emu-myc model of B-cell lymphoma. These transgenic models have allowed us to distinguish the role of pfp in surveillance of B-cell lymphomagenesis, as opposed to its loss simply driving the onset of a spontaneous lymphoma characteristic of pfp deficiency.
Bolitho
Paul
P
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
Street
Shayna E A
SE
Westwood
Jennifer A
JA
Edelmann
Winfried
W
Macgregor
Duncan
D
Waring
Paul
P
Murray
William K
WK
Godfrey
Dale I
DI
Trapani
Joseph A
JA
Johnstone
Ricky W
RW
Smyth
Mark J
MJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D016374:Oncogene Proteins v-abl / Q000235:genetics; D054353:Perforin / Q000502:physiology*; D010954:Plasmacytoma / Q000235:genetics; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D016374:Oncogene Proteins v-abl; D016159:Tumor Suppressor Protein p53; D054353:Perforin; D000070957:MutL Protein Homolog 1