Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas.
The transcription factor YB-1 is expressed in a wide range of cell types and has been implicated in the regulation of various genes involved in cell proliferation. Nuclear expression of YB-1 is correlated with MDR-1 gene expression in breast cancer and osteosarcoma. In this study, we asked whether YB-1 expression is enhanced in human colorectral carcinoma and if it is associated with the expression of target genes such as MDR-1, DNA topoisomerase II alpha and PCNA. YB-1, DNA topoisomerase II alpha, PCNA and MDR-1 expression were assessed by Western blotting, Northern blotting and immunohistochemistry in 26 human colorectal carcinomas. The involvement of YB-1 in DNA topoisomerase II alpha gene expression was examined by transient DNA transfection assays. YB-1 was overexpressed in almost all cancerous lesions in comparison with normal mucosa in surgically resected colorectal carcinomas of 26 patients. YB-1 expression correlated well with both DNA topoisomerase II alpha and PCNA expression. In contrast, no correlation was observed between YB-1 and MDR-1 expression. We also found that a transient co-transfection with a DNA topoisomerase II alpha promoter-luciferase plasmid and an antisense YB-1 expression construct resulted in a significant reduction of the promoter activity in KM12C human colon cancer cells. YB-1 may be an excellent proliferation-associated marker and may be a transcription factor regulating DNA topoisomerase II alpha gene expression in human colorectal carcinoma.
Shibao
K
K
Department of Surgery I, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Takano
H
H
Nakayama
Y
Y
Okazaki
K
K
Nagata
N
N
Izumi
H
H
Uchiumi
T
T
Kuwano
M
M
Kohno
K
K
Itoh
H
H
D000368:Aged; D000951:Antigens, Neoplasm; D003110:Colonic Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D051840:Y-Box-Binding Protein 1
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004250:DNA Topoisomerases, Type II