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Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in breast cancer

Hideaki Dote1, Shinichi Toyooka, Kazunori Tsukuda

  • 1Department of Cancer, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 26, 2004
PubMed
Abstract

Insights

Aberrant methylation of the human DOC-2/DAB2 interactive protein (hDAB2IP) gene frequently occurs in breast cancer, leading to gene inactivation. This methylation is linked to lymph node metastasis, suggesting hDAB2IP

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The human DOC-2/DAB2 interactive protein (hDAB2IP) gene acts as a tumor suppressor.
  • hDAB2IP inactivation via methylation is observed in prostate cancer.
  • The role of hDAB2IP in breast cancer requires further investigation.

Purpose of the Study:

  • To analyze the methylation and expression status of hDAB2IP in breast cancer.
  • To develop and apply methylation-specific PCR assays for hDAB2IP in breast cancer samples.

Main Methods:

  • Bisulfite DNA sequencing was used to assess hDAB2IP promoter methylation in two regions (m2a and m2b) in breast cancer cell lines.
  • Real-time reverse transcription-PCR quantified hDAB2IP expression.
  • Methylation-specific PCR assays were developed and applied to cell lines and primary tumors.
  • 5-aza-2'-deoxycytidine treatment was used to confirm the effect of methylation on gene expression.

Main Results:

  • Aberrant methylation of hDAB2IP was detected in 44-48% of breast cancer cell lines and 33-38% of primary tumors.
  • Methylation showed an inverse correlation with hDAB2IP gene expression.
  • Gene expression was restored upon treatment with 5-aza-2'-deoxycytidine, confirming methylation-induced silencing.
  • hDAB2IP methylation in the m2b region was associated with advanced nodal status in primary breast tumors.

Conclusions:

  • Methylation-specific PCR assays for hDAB2IP were successfully developed and utilized in breast cancer.
  • Frequent hDAB2IP methylation contributes to gene inactivation in breast cancer.
  • hDAB2IP methylation is implicated in the lymph node metastasis of breast cancer.

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