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

Int J Cancer. 1999 Dec 10;83(6):732-7. doi: 10.1002/(sici)1097-0215(19991210)83:6<732::aid-ijc6>3.0.co;2-#.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm
  • Colonic Neoplasms / genetics*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • DNA Topoisomerases, Type II* / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic*
  • Genes, MDR
  • Humans
  • Isoenzymes / genetics*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen / genetics
  • Recombinant Proteins / metabolism
  • Rectal Neoplasms / genetics*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transfection
  • Y-Box-Binding Protein 1


  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Isoenzymes
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • Recombinant Proteins
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • DNA Topoisomerases, Type II