IκBα Overexpression Delays Tumor Formation in v-rel Transgenic Mice

Abstract

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 κB-binding activity. Since experimental evidence has led to the suggestion of a potential tumor suppressor activity for IκBα, we have studied the role of IκBα in the transforming activity of v-Rel by overexpressing IκBα in v-rel transgenic mice. Overexpression of IκBα 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 IκBα may be a key element in its transforming capability.