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

The highly conserved protein p27(BBP) is a cytoplasmic interactor of integrin β4 expressed in epithelia, p27(BBP) is found in two pools: one nuclear pool enriched in the perinucleolar region, and one cytoplasmic pool. Deletion of p27(BBP) in yeast is lethal as a result of loss of the ribosomal 60S subunit. The aim of this study was to investigate the distribution of p27(BBP) in gut epithelium and its behavior during progression of human colorectal carcinomas. Results indicated that p27(BBP) is high in rapidly cycling cells and decreased in villous cells committed to apoptotic cell death. In dysplastic adenomas and carcinomas, p27(BBP) displayed a large increase of its nucleolar component that was superimposable to argyrophylic nucleolar organizing region-associated proteins and was associated with the nuclear matrix. Western blotting confirmed increased p27(BBP) in dysplastic adenomas 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 carcinomas, supporting the idea of transcriptional or post-transcriptional regulation of its expression. Results suggested that p27(BBP) alterations are an early event in the transition from benign to malignant colorectal phenotypes and provide a novel tool in surgical pathology.