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Expression of a Highly Conserved Protein, p27^BBP, during the Progression of Human Colorectal Cancer¹

San Raffaele Scientific Institute, 20132 Milan [F. S., F. Vi., S. G., G. S., M. C., E. V., F. Ve., A. D., P. C. M.], and Department of Medical Sciences, University of Eastern Piedmont, 28100 Novara [S. B.], Italy

The highly conserved protein p27^BBP is a cytoplasmic interactor of integrin ß4 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.

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