Transformation of T lymphocytes by the v-fos oncogene.
Activation of T lymphocytes through the T cell antigen receptor has been shown to stimulate a rapid and transient accumulation of c-fos mRNA and protein. Transfection of a normal murine T lymphocyte clone with the FBJ-v-fos oncogene resulted in generation of a cell line that was morphologically transformed, had lost the requirement for IL-2 for proliferation, and was tumorigenic in adult syngeneic mice; however, the transformed cells retained the ability to proliferate in response to IL-2. The transformed cells did not show constitutive expression of IL-2 or c-fos mRNA, although the promoter regions of both IL-2 and c-fos genes contain AP-1 sites that are expected to be targets for binding of Fos/Jun complexes. In contrast, the transformed T cells showed increased constitutive expression of IL-2R alpha and c-myc mRNA; these genes may represent cellular targets for transformation by v-fos and physiologic activation by c-fos. We discuss the possibility that these transformed cells behave as cells partially activated through the TCR, and that transformation occurs through a mechanism independent of IL-2.
Valge-Archer
V E
VE
Division of Tumor Virology, Dana Farber Cancer Institute, Boston, MA 02115.
de Villiers
J
J
Sinskey
A J
AJ
Rao
A
A
D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002472:Cell Transformation, Viral; D015870:Gene Expression; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D016761:Oncogene Proteins v-fos; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology
D007376:Interleukin-2; D016761:Oncogene Proteins v-fos; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger