Fas-independent apoptosis in T-cell tumours induced by the CD2-myc transgene.
Depending on the cellular context, the Myc oncoprotein is capable of promoting cell proliferation or death by apoptosis. These observations suggest that apoptosis in response to deregulated gene expression may represent a natural brake to tumour development. The pathways by which Myc induces apoptosis are as yet poorly characterised although recent observations on rat fibroblasts over-expressing Myc have demonstrated a requirement for the Fas pathway. To investigate the role of Fas in Myc-induced lymphomagenesis we backcrossed CD2-myc mice onto an lpr background. Rates of tumour development and phenotypic properties, including levels of apoptosis were indistinguishable from CD2-myc controls. Further, tumour cell lines derived from mice expressing a regulatable form of Myc showed inducible apoptosis at similar rates regardless of their lpr genotype. These results show that activation of c-myc and loss of Fas do not collaborate in T lymphoma development and that Myc-induced apoptosis in T-cells occurs by Fas-independent pathways.
Cameron
E R
ER
Molecular Oncology Laboratory, Glasgow University Veterinary School, Bearsden Road, Glasgow, G61 1QH, UK. E.R.Cameron@vet.gla.ac.uk
Morton
J
J
Johnston
C J
CJ
Irvine
J
J
Bell
M
M
Onions
D E
DE
Neil
J C
JC
Campbell
M
M
Blyth
K
K
D000818:Animals; D017209:Apoptosis; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D005260:Female; D009052:Leukemia Virus, Murine / Q000235:genetics; D008223:Lymphoma; D016399:Lymphoma, T-Cell / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011533:Proviruses / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016662:Virus Integration; D019014:fas Receptor / Q000378:metabolism*
D018801:CD2 Antigens; D016271:Proto-Oncogene Proteins c-myc; D019014:fas Receptor