Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas

The transcription factor YB-I is expressed in a wide range of cell types an d has been implicated in the regulation of various genes involved in cell p roliferation. Nuclear expression of YB-I is correlated with MDR-I gene expr ession in breast cancer and osteosarcoma, In this study, we asked whether Y B-I expression is enhanced in human colorectral carcinoma and if it is asso ciated with the expression of target genes such as MDR-I, DNA topoisomerase II alpha and PCNA, YB-I, DNA topoisomerase II alpha, PCNA and MDR-I expres sion were assessed by Western blotting, Northern blotting and immunohistoch emistry in 26 human colorectal carcinomas, The involvement of YB-I in DNA t opoisomerase II alpha gene expression was examined by transient DNA transfe ction assays. YB-I was overexpressed in almost all cancerous lesions in com parison with normal mucosa in surgically resected colorectal carcinomas of 26 patients, YB-I expression correlated well with both DNA topoisomerase II alpha and PCNA expression. In contrast, no correlation was observed betwee n YB-I and MDR-I expression, We also found that: a transient: co-transfecti on with a DNA topoisomerase II alpha promoter-luciferase plasmid and an ant isense YB-I expression construct resulted in a significant reduction of the promoter activity in KM12C human colon cancer cells, YB-I may be an excell ent proliferation-associated marker and may be a transcription factor regul ating DNA topoisomerase II or gene expression in human colorectal carcinoma . (C) 1999 Wiley-Liss, Inc.