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 (Eμ)-v-Abl, Eμ-myc, and vav-bcl2]. Pfp was shown...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-02, Vol.106 (8), p.2723-2728
Main Authors: Bolitho, Paul, Street, Shayna E.A, Westwood, Jennifer A, Edelmann, Winfried, MacGregor, Duncan, Waring, Paul, Murray, William K, Godfrey, Dale I, Trapani, Joseph A, Johnstone, Ricky W, Smyth, Mark J
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Animals
Biological Sciences
Effects
Gene expression
Lymphoma
Lymphoma, B-Cell - genetics
Lymphoma, B-Cell - physiopathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
MutL Protein Homolog 1
Nuclear Proteins - genetics
Oncogene Proteins v-abl - genetics
Perforin - physiology
Plasmacytoma - genetics
Rodents
Studies
Transplantation, Heterologous
Tumor Suppressor Protein p53 - genetics
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Summary: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 (Eμ)-v-Abl, Eμ-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 Eμ-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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0809008106