title: Perforin-mediated suppression of B-cell lymphoma.
abstract: 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.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Bolitho
authors.forename: Shayna E A
authors.initials: SE
authors.lastname: Street
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Westwood
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
authors.forename: Duncan
authors.initials: D
authors.lastname: Macgregor
authors.forename: Paul
authors.initials: P
authors.lastname: Waring
authors.forename: William K
authors.initials: WK
authors.lastname: Murray
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: 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
chemical_list: 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