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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues

Satoshi Ikeda1, Jyoji Imura2, Keiko Suzuki1

  • 1Department of Pathology, Tsuchiura Kyodo General Hospital, Ibaraki 300-0053;

Molecular and Clinical Oncology
|March 21, 2014
PubMed

Insights

DNA methyltransferase 1 (DNMT1) overexpression correlates with endometrial cancer progression and the silencing of tumor suppressor genes hMLH1 and E-cadherin. DNMT1 expression is a useful marker for identifying methylation-related conditions in clinical samples.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Gene methylation is crucial in carcinogenesis, often inactivating tumor suppressor genes.
  • DNA methyltransferase 1 (DNMT1) is a key enzyme in DNA methylation.
  • Endometrial cancers frequently show inactivation of genes like hMLH1 and E-cadherin.

Purpose of the Study:

  • To investigate DNA methyltransferase 1 (DNMT1) expression in normal and cancerous endometrial tissues.
  • To correlate DNMT1 expression with tumor progression and the expression of hMLH1 and E-cadherin.
  • To explore the role of DNMT1 gene amplification in protein overexpression.

Main Methods:

  • Analysis of DNMT1, hMLH1, and E-cadherin expression in endometrial tissue samples (normal, hyperplasia, atypical hyperplasia, carcinoma).
  • Correlation studies between DNMT1 expression and clinicopathological features.
  • Assessment of DNMT1 gene amplification and its relation to protein levels.

Main Results:

  • DNMT1 expression significantly correlated with endometrial tumor progression (P=0.0023).
  • DNMT1 expression was associated with reduced hMLH1 and E-cadherin expression (P=0.031).
  • DNMT1 overexpression, particularly mRNA, was prevalent in carcinomas, linked to gene amplification (P=0.041).

Conclusions:

  • DNMT1 expression serves as a valuable indicator for methylation-associated conditions in clinical settings.
  • Overexpression of DNMT1 protein in endometrial cancer is multifactorial, including gene amplification.
  • DNMT1 plays a significant role in endometrial carcinogenesis by influencing tumor suppressor gene silencing.
Keywords:
DNA methyltransferase 1E-cadherinendometrial cancerhMLH1in situ hybridization

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