IkappaBalpha overexpression delays tumor formation in v-rel transgenic mice.
We have previously shown that transgenic mice expressing the oncoprotein v-Rel under the control of a T cell-specific promoter develop T cell lymphomas. Tumor formation was correlated with the presence of p50/v-Rel and v-Rel/v-Rel nuclear kappaB-binding activity. Since experimental evidence has led to the suggestion of a potential tumor suppressor activity for IkappaBalpha, we have studied the role of IkappaBalpha in the transforming activity of v-Rel by overexpressing IkappaBalpha in v-rel transgenic mice. Overexpression of IkappaBalpha in v-rel transgenic mice resulted in an extended survival, and the development of cutaneous T cell lymphomas of CD8(+)CD4(-) phenotype. These phenotypic alterations were associated with a dramatic reduction of p50/v-Rel, but not v-Rel/v-Rel nuclear DNA binding activity and an increased expression of the intercellular adhesion molecule 1. Our results indicate that v-Rel homodimers are active in transformation and that the capacity of v-Rel-containing complexes to escape the inhibitory effect of IkappaBalpha may be a key element in its transforming capability.
Carrasco
D
D
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Perez
P
P
Lewin
A
A
Bravo
R
R
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D005434:Flow Cytometry; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000517:prevention & control*; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA