Reversible activation of c-Myc in thymocytes enhances positive selection and induces proliferation and apoptosis in vitro.
In order to study the effect of c-Myc activation in T lymphocytes in vivo, we generated transgenic mice that express a 4-hydroxytamoxifen (4-OHT)-dependent switchable c-myc oncoprotein under the control of the proximal lck promoter. Activation of c-MycER causes no obvious alteration in T cell ontogeny. However, using MHC class I restricted H-Y-TCR transgenic mice, we found that c-Myc activation in vivo enhances the efficiency of positive selection. Moreover, splenic T cells derived from lck-c-mycER transgenic mice in which c-Myc had been activated exhibited increased proliferation in vitro in response to activation with anti-CD3/CD28 antibody. Activation of c-MycER also promotes apoptosis in thymocytes in vitro.
Rudolph
B
B
Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Hueber
A O
AO
Evan
G I
GI
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
D013629:Tamoxifen; C016601:afimoxifene