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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

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Insulin-like growth factor 2 expression in prostate cancer is regulated by promoter-specific methylation

Stefan Küffer1, Tobias Gutting2,3, Djeda Belharazem2

  • 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, Germany.

Molecular Oncology
|December 15, 2017
PubMed

Insights

Insulin-like growth factor 2 (IGF2) is downregulated in most prostate cancers (PCa), contrary to other tumors. This decrease is linked to promoter methylation, not imprinting changes, suggesting new therapeutic targets for PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The insulin-like growth factor (IGF) axis is implicated in various cancers.
  • IGF2, a key growth factor, plays a role in malignancies, but its regulation in prostate cancer (PCa) is unclear.
  • Loss of imprinting (LOI) typically increases IGF2, but its role in PCa is not well understood.

Purpose of the Study:

  • Investigate the expression patterns and regulatory mechanisms of IGF2 in prostate cancer.
  • Determine the role of IGF2 imprinting and promoter methylation in PCa development.
  • Identify potential therapeutic targets within the IGF2 pathway for PCa treatment.

Main Methods:

  • Quantitative analysis of IGF2 mRNA and protein levels in PCa tissues and adjacent normal prostate tissues.
  • Assessment of IGF2 imprinting status (LOI) in tumor samples.
  • Analysis of DNA methylation patterns in IGF2 promoters (P3 and P4) using methylation-specific techniques.

Main Results:

  • IGF2 expression was decreased in 80% of PCa compared to adjacent prostate tissue, independent of LOI status.
  • IGF2 expression primarily utilized promoters P3 and P4 in both tumor and normal tissues.
  • Hypermethylation of IGF2 promoters P3 and P4 correlated with decreased IGF2 expression in most PCa.
  • Specific methylation in promoter P4's A region was associated with increased IGF2 in the remaining 20% of PCa.

Conclusions:

  • IGF2 is predominantly downregulated in prostate cancer, primarily through promoter-specific methylation, differing from other tumor types.
  • Altered IGF2 expression may be relevant in early PCa development and during specific treatments like chemotherapy and androgen deprivation.
  • Targeting IGF2 promoter regions presents a potential strategy for adjuvant therapy in prostate cancer.
Keywords:
IGF2imprintingpromoter methylationprostate cancertargeted therapy

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