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