IκBα Overexpression Delays Tumor Formation in v-rel Transgenic Mice

Summary 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 k B-binding activity. Since experimental evidence has led to the suggestion of a potential tumor suppressor activity for I k B a , we have studied the role of I k B a in the transforming activity of v-Rel by overexpressing I k B a in v- rel transgenic mice. Overexpression of I k B a in v- rel transgenic mice resulted in an extended survival, and the development of cutaneous T cell lymphomas of CD8 1 CD4 2 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 k B a may be a key element in its transforming capability.