Journal article
Perforin-mediated suppression of B-cell lymphoma
P Bolitho, SEA Street, JA Westwood, W Edelmann, D MacGregor, P Waring, WK Murray, DI Godfrey, JA Trapani, RW Johnstone, MJ Smyth
Proceedings of the National Academy of Sciences of the United States of America | Published : 2009
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 (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..
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Funding Acknowledgements
We acknowledge Dr. Jerry Adams and Dr. Alan Harris for their generous gift of the transgenic mouse strains used in this study. We also thank our colleagues in the Cancer Immunology Program and the staff of the Peter MacCallum Cancer Centre animal facility and the microscopy imaging and research core facility for valuable technical assistance and intellectual advice that has contributed to this work. We acknowledge Robert D. Schreiber of the Washington University School of Medicine for critical review of this manuscript. P. B. is supported by a Cancer Research Institute Predoctoral Emphasis in Tumor Immunology Scholarship. D. I. G., R.W.J., and M.J.S. are supported by Research Fellowships and a Program Grant from the National Health and Medical Research Council of Australia.