Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycER mice.
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-mycER) 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-mycER 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.
Blyth
K
K
Molecular Oncology Laboratory, University of Glasgow Veterinary School, Bearsden.
Stewart
M
M
Bell
M
M
James
C
C
Evan
G
G
Neil
J C
JC
Cameron
E R
ER
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018801:CD2 Antigens / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005813:Genes, Synthetic; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D020287:In Situ Nick-End Labeling; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology*
D018801:CD2 Antigens; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen; C016601:afimoxifene