K. Shibao et al., Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas, INT J CANC, 83(6), 1999, pp. 732-737
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.