Decreased expression of insulin-like growth factor binding protein 7 in human colorectal carcinoma is related to DNA methylation

  • Fei Ye
  • Yuan Chen
  • Thomas Knösel
  • Karsten Schlüns
  • Manuela Pacyna-Gengelbach
  • Nicole Deutschmann
  • Maode Lai
  • Iver Petersen
Original Paper

DOI: 10.1007/s00432-006-0171-z

Cite this article as:
Ye, F., Chen, Y., Knösel, T. et al. J Cancer Res Clin Oncol (2007) 133: 305. doi:10.1007/s00432-006-0171-z

Abstract

Purpose

Insulin-like growth factor binding protein 7 (IGFBP-7) is considered a tumor suppressor in various cancers, but its role in colorectal cancer (CRC) is still uncertain. The aims of this study were to analyze the IGFBP-7 expression, and explore the mechanism responsible for the inactivation of IGFBP-7 in CRC.

Methods

mRNA expression was studied by RT-PCR and Northern blot analysis of cultured cells. Methylation status was analyzed by treatment with 5-aza-2′-deoxycytidine followed by sequencing of PCR products of sodium bisulfite-treated genomic DNA. IGFBP-7 protein expression was evaluated by immunohistochemistry (IHC) on tissue microarrays.

Results

mRNA expression was lost in six out of eight CRC cell lines as compared to normal colon cells. DNA methylation was found in the region of exon 1 and intron 1 of IGFBP-7. In tumor tissue, 107 out of 279 samples showed a negative expression of IGFBP-7 by IHC, which was significantly associated with poor prognosis. The analysis of 37 paired cancerous and normal mucosa samples confirmed the downregulation in the tumors, but revealed variable basal expression levels of IGFBP-7 in normal mucosal samples.

Conclusions

DNA methylation is a mechanism responsible for IGFBP-7 gene silencing providing a target for therapeutic intervention of this tumor suppressor gene.

Keywords

IGFBP-7 mRNA expression Protein expression DNA methylation Tissue microarrays CRC 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Fei Ye
    • 1
  • Yuan Chen
    • 1
  • Thomas Knösel
    • 1
  • Karsten Schlüns
    • 1
  • Manuela Pacyna-Gengelbach
    • 1
  • Nicole Deutschmann
    • 1
  • Maode Lai
    • 2
  • Iver Petersen
    • 1
    • 3
  1. 1.Institute of PathologyCharité University Medicine Berlin—Campus MitteBerlinGermany
  2. 2.Department of Pathology, School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China
  3. 3.Institute of Pathology, Charité—Campus MitteHumboldt-UniversityBerlinGermany

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