The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/279/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 2, July 21, 1997 279-288

Article

I{kappa}B{alpha} Overexpression Delays Tumor Formation in v-rel Transgenic Mice

Daniel Carrasco, Paloma Perez, Anne Lewin, and Rodrigo Bravo

From the Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

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.

Address correspondence to Rodrigo Bravo, Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000. Phone: 609-252-5744; FAX: 609-252-3307; E-mail: Bravo#m#_Rodrigo.PRILVMS1{at}msmail.bms.com

1Abbreviations used in this paper: EMSA, electrophoretic mobility shift assay; ICAM-1, intercellular adhesion molecule 1; mRNA, messenger RNA; RHD, Rel homology domain.

These studies were performed according to guidelines established by the Bristol-Myers Squibb Animal Care and Use Committee.


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