Differences in sensitivity to induction of apoptosis among rat fibroblast cells transformed by HTLV-I tax gene or cellular nuclear oncogenes.
The tax gene of human T lymphotropic virus type I has been implicated in the genesis of adult T cell leukemia (ATL). It has been reported that expression of tax induces neoplastic transformation in the rat fibroblast cell line Rat-1, and that co-expression with the ras gene can transform rat embryo fibroblasts. Possible activation of cellular oncogenes including c-myc and c-fos by tax has been implicated in these tax functions. In this study, comparative analysis of biological properties of tax and cellular nuclear oncogenes c-myc and c-fos was performed in Rat-1 cells. While all three oncogenes could transform Rat-1 cells, significant differences in the sensitivity to induction of apoptosis were observed between cells transformed with each oncogene. Induction of apoptosis by serum starvation was observed in tax-transfected Rat-1 cells but to a lesser extent than that in those transfected with c-myc or c-fos. In contrast, exposure to a DNA-damaging agent, etoposide, resulted in enhanced apoptotic death only in c-myc-transfected Rat-1 cells. Our findings indicate that the pathways for apoptosis induction may not be identical among these three oncogenes, and that the relatively low apoptosis-inducing activity and sufficient transforming capacity of tax might be associated with transformation of T cells and the low susceptibility of the transformed T cells (ATL cells) to chemotherapeutic agents.
Fujita
M
M
Department of Oncology, Nagasaki University School of Medicine, Japan.
Shiku
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002467:Cell Nucleus; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D016895:Culture Media, Serum-Free; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts; D016762:Genes, fos; D016259:Genes, myc; D016158:Genes, p53; D016355:Genes, pX / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051381:Rats
D016895:Culture Media, Serum-Free; D005047:Etoposide