Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycERTM mice

Blyth, K. , Stewart, M., Bell, M., James, C., Evan, G., Neil, J. C. and Cameron, E. R. (2000) Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycERTM mice. Oncogene, 19(6), pp. 773-782. (doi:10.1038/sj.onc.1203321) (PMID:10698495)

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Abstract

To study the effects of the Myc oncoprotein in a regulatable in vivo system, we generated lines of transgenic mice in which a tamoxifen inducible Myc fusion protein (c-mycERTM) is expressed under the control of the CD2 locus control region. Activation of the Myc oncoprotein resulted in both proliferation and apoptosis in vivo. Lines with a high transgene copy number developed spontaneous lymphomas at low frequency, but the tumour incidence was significantly increased with tamoxifen treatment. Surprisingly, we found that cellular sensitivity to Myc-induced apoptosis was retained in tumours from these mice and in most lymphoma cell lines, even when null for p53. Resistance to Myc-induced apoptosis could be conferred on these cells by co-expression of Bcl-2. However, acquired resistance is clearly not an obligatory progression event as sensitivity to apoptosis was retained in transplanted tumours in athymic mice. In conclusion, lymphomas arising in CD2-mycERTM mice retain the capacity to undergo apoptosis in response to Myc activation and show no phenotypic evidence of the presence of an active dominant inhibitor.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bell, Mrs Margaret and Blyth, Dr Karen and Cameron, Professor Ewan and Stewart, Dr Monica and Neil, Professor James
Authors: Blyth, K., Stewart, M., Bell, M., James, C., Evan, G., Neil, J. C., and Cameron, E. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594

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