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Loss of LDOC1 expression by promoter methylation in cervical cancer cells

Marie-Luise Buchholtz1, Julia Jückstock, Elena Weber

  • 1Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany.

Cancer Investigation
|October 16, 2013
PubMed

Insights

Loss of the LDOC1 tumor suppressor is frequent in cervical cancer, often due to promoter methylation. This silencing may serve as a valuable molecular marker for cervical cancer progression and treatment response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cervical cancer lacks reliable prognostic factors for disease progression and response to chemotherapy.
  • The role of the LDOC1 tumor suppressor candidate in cervical cancer is not well understood.

Purpose of the Study:

  • To investigate the expression of the LDOC1 tumor suppressor candidate in cervical cancer.
  • To determine the mechanism of LDOC1 downregulation and its potential as a molecular marker.

Main Methods:

  • Analysis of LDOC1 expression in cervical cancer cell lines and patient biopsies.
  • PCR-based promoter methylation analysis.
  • Treatment with DNA methyltransferase inhibitors to assess reversibility of silencing.

Main Results:

  • LDOC1 expression was silenced in four out of six tested cervical cancer cell lines.
  • Downregulation of LDOC1 was observed in cervical cancer tissue specimens.
  • A significant association was found between LDOC1 promoter methylation and loss of LDOC1 expression.
  • Silencing of LDOC1 was reversible upon treatment with DNA methyltransferase inhibitors.

Conclusions:

  • LDOC1 silencing is a frequent event in cervical cancer.
  • Promoter methylation is a key mechanism for LDOC1 silencing in cervical cancer.
  • LDOC1 may represent a potential molecular marker for cervical cancer prognosis and therapeutic targeting.

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