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Updated: Jul 18, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Published on: August 5, 2022

Frequent epigenetic inactivation of cystatin M in breast carcinoma

U Schagdarsurengin1, G P Pfeifer, R Dammann

  • 1AWG Tumour Genetics of the Medical Faculty, Institute for Human Genetics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.

Oncogene
|November 14, 2006
PubMed

Insights

Cystatin M, an inhibitor of proteases, is epigenetically silenced in breast cancer, suppressing tumor growth. Reactivating its expression may offer a new therapeutic strategy for breast carcinoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Epigenetics

Background:

  • Cystatin M is an endogenous inhibitor of lysosomal cysteine proteases.
  • Downregulation of cystatin M expression is observed in breast carcinoma.
  • Previous studies indicate cystatin M suppresses breast cancer cell growth and migration.

Purpose of the Study:

  • To investigate the epigenetic inactivation of cystatin M in breast cancer.
  • To determine the effect of cystatin M re-expression on breast carcinoma growth.

Main Methods:

  • Combined bisulphite restriction analysis was used to examine cystatin M promoter methylation in breast cancer cell lines and primary tumors.
  • Breast cancer cells were treated with 5-aza-2'-deoxycytidine (5-Aza-CdR) to reactivate cystatin M transcription.
  • Cystatin M was transfected into T47D cells to assess its impact on colony formation.

Main Results:

  • The cystatin M promoter was highly methylated in all tested breast cancer cell lines.
  • Primary breast tumors showed significantly higher methylation frequency (60%) compared to normal tissues (25%).
  • 5-Aza-CdR treatment reactivated cystatin M transcription, and cystatin M transfection decreased colony formation by 30%.

Conclusions:

  • Cystatin M is frequently epigenetically inactivated during breast carcinogenesis.
  • Cystatin M expression suppresses breast carcinoma growth, suggesting its role as a tumor suppressor gene.
  • Epigenetic reactivation of cystatin M could be a potential therapeutic approach for breast cancer.

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