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Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
11:02

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

Epigenetic CRBP downregulation appears to be an evolutionarily conserved (human and mouse) and oncogene-specific

Alice Arapshian1, Silvina Bertran, Yuvarani S Kuppumbatti

  • 1Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. aa74ny@yahoo.com

Molecular Cancer
|April 29, 2004
PubMed
Abstract

Insights

Cellular retinol binding protein I (CRBP) is epigenetically silenced by DNA hypermethylation in breast cancer. This conserved mechanism contributes to tumor progression and may be linked to specific oncogenes.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Cellular retinol binding protein I (CRBP) gene downregulation is observed in human breast cancers and mouse models.
  • CRBP downregulation is implicated in breast tumor progression.
  • The epigenetic mechanisms driving CRBP silencing in cancer remain largely unknown.

Purpose of the Study:

  • To investigate the hypothesis that CRBP is epigenetically silenced through DNA hypermethylation in human and mouse breast cancer.
  • To determine the relationship between CRBP hypermethylation and CRBP expression.
  • To explore potential therapeutic strategies for reversing CRBP silencing.

Main Methods:

  • Bisulfite sequencing of the CRBP gene in human breast cancer cell lines and mouse mammary tumor cell lines.
  • Treatment with 5-azacytidine (DNA methyltransferase inhibitor) and trichostatin A (histone deacetylase inhibitor).
  • Southern blot analysis of human breast cancer specimens.

Main Results:

  • CRBP hypermethylation was inversely correlated with CRBP expression in most human breast cancer cell lines.
  • 5-azacytidine treatment restored CRBP expression, confirming DNA hypermethylation as a cause of silencing.
  • CRBP hypermethylation and silencing were observed in MMTV-Myc mouse models, suggesting an oncogene-specific event.

Conclusions:

  • CRBP hypermethylation is a conserved and primary mechanism for CRBP gene silencing in breast cancer.
  • CRBP silencing in human breast cancer may be associated with specific oncogenic signatures.
  • Targeting epigenetic modifications offers potential therapeutic avenues for breast cancer treatment.

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