Journal article
Pharmacological blockade of Bcl-2, Bcl-x L and Bcl-w by the BH3 mimetic ABT-737 has only minor impact on tumour development in p53-deficient mice
S Grabow, P Waring, L Happo, M Cook, KD Mason, PN Kelly, A Strasser
Cell Death and Differentiation | Published : 2012
DOI: 10.1038/cdd.2011.133
Abstract
The tumour suppressor p53 transcriptionally regulates a range of target genes that control cell growth and survival. Mutations of p53 have been implicated in the development of ∼50% of human cancers, including those instigated by exposure to mutagens. Although numerically rare, cancers can arise as a consequence of inherited mutations, such as in the Li-Fraumeni syndrome, which is caused by mutation of one p53 allele. Gene-targeted mice deficient for p53 have been generated to study this familial cancer syndrome. On a C57BL/6 background, p53-deficient mice develop primarily thymic lymphoma and more rarely sarcoma. Evasion of apoptosis is considered to be essential for neoplastic transformati..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Abbott Laboratories and Genentech Inc. for providing us with ABT-737; Dr. T Jacks for p53-deficient mice; Drs. LA O'Reilly and DC Huang, and Mr. ARD Delbridge, for advice and reagents; K McKenzie, G Siciliano, N Iannarella, L Reid and K Vella for expert animal care; B Helbert and C Young for genotyping; J Corbin for automated blood analysis; E Tsui, V Babo, K Weston, Y Hoang and S Hasanein for histology, and D Quilici, T Nikolaou and G Thomas for gamma-irradiation. This work was supported by grants and fellowships from the Cancer Council of Victoria (to PNK), the National Health and Medical Research Council (Program Grant no. 461221; NHMRC Australia Fellowship), the NIH (CA43540) and the Leukemia and Lymphoma Society (SCOR Grant no. 7413), University of Melbourne International Research Scholarship, University of Melbourne International Fee Remission Scholarship, Cancer Therapeutics CRC Top-up Scholarship (last three to SG) and operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.