Expression of a highly conserved protein, p27(BBP), during the progressionof human colorectal cancer

The highly conserved protein p27(BBP) is a cytoplasmic interactor of integr in beta 4 expressed in epithelia, p27(BBP) is found in two pools: one nucle ar pool enriched in the perinucleolar region, and one cytoplasmic pool. Del etion of p27(BBP) in yeast is lethal as a result of loss of the ribosomal 6 0S subunit, The aim of this study was to investigate the distribution of p2 7(BBP) in gut epithelium and its behavior during progression of human color ectal carcinomas. Results indicated that p27(BBP) is high in rapidly cyclin g cells and decreased in villous cells committed to apoptotic cell death. I n dysplastic adenomas and carcinomas, p27(BBP) displayed a large increase o f its nucleolar component that was superimposable to argyro-phylic nucleola r organizing region-associated proteins and was associated with the nuclear matrix. Western blotting confirmed increased p27(BBP) in dysplastic adenom as and in carcinomas. In particular, p27(BBP) increased progressively from adenomas to carcinomas and, in the latter, was related to the tumor stage. The overexpression of p27(BBP) corresponded to mRNA up-regulation in carcin omas, supporting the idea of transcriptional or post-transcriptional regula tion of its expression. Results suggested that p27(BBP) alterations are an early event in the transition from benign to malignant colorectal phenotype s and provide a novel tool in surgical pathology.