Expression of the stress-associated protein p8 is a requisite for tumor development.

Abstract

We identified a new gene, called p8, because its expression was strongly induced during the acute phase of pancreatitis. Further experiments have shown that p8 mRNA is activated in response to several stresses and that its activation is not restricted to pancreatic cells. p8 is a nuclear protein and biochemical and biophysical studies have shown that p8 was very similar in many structural aspects to the HMG proteins, although sharing only low amino acid sequence homology. Also, p8 was found overexpressed in many human cancers. Therefore, we wondered whether the p8-mediated response to cellular stress was necessary for tumor establishment. Subcutaneous or intraperitoneal injections of transformed p8-expressing fibroblasts led to tumor formation in nude mice, but no tumor was observed with transformed p8-deficient cells. Restoring p8 expression in transformed p8-deficient fibroblasts led to tumor formation, demonstrating that p8 expression is crucial for tumor development and suggesting that the stress-response mechanisms governed by p8 are required for tumor establishment.