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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

Estrogen receptor α regulates ATM Expression through miRNAs in breast cancer

Xiaojing Guo1, Chunying Yang, Xiaolong Qian

  • 1Authors' Affiliations: Department of Breast Pathology and Lab, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Departments of Radiation Oncology, and Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas; and Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 17, 2013
PubMed
Abstract

Insights

Estrogen receptor α (ERα) normally suppresses ATM kinase in breast cancer. Its absence in ER-negative tumors leads to higher ATM, increasing recurrence risk after radiotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Estrogen receptor α (ERα) plays a key role in mammary gland development and breast cancer.
  • ER-negative breast cancers often exhibit aggressive behavior and resistance to therapies.
  • Mechanisms underlying the aggressive phenotype of ER-negative tumors are not fully understood.

Purpose of the Study:

  • To investigate the role of ERα in regulating ATM expression in breast cancer.
  • To explore the involvement of microRNAs (miRNAs) in the ERα-ATM regulatory pathway.
  • To determine the correlation between ATM expression and radiotherapy outcomes in breast cancer patients.

Main Methods:

  • Immunohistochemistry on 296 breast cancer tissues.
  • siRNA knockdown to assess ERα's effect on ATM expression in cell lines.
  • miRNA manipulation (antisense oligonucleotides and overexpression plasmids) to study miR-18a and -106a.
  • In situ hybridization to evaluate miR-18a and -106a expression in tissues.

Main Results:

  • ATM kinase, a DNA damage-response protein, is upregulated in ER-negative breast cancer tissues.
  • Higher ATM expression correlates with increased locoregional recurrence rates after radiotherapy.
  • ERα negatively regulates ATM expression, partly through activating miR-18a and -106a.
  • miR-18a and -106a are significantly underexpressed in ER-negative breast cancer tissues.

Conclusions:

  • A novel regulatory mechanism involving ERα, miR-18a, miR-106a, and ATM in breast cancer is identified.
  • This pathway offers potential therapeutic targets for ER-negative breast cancers.
  • Understanding this mechanism may improve radiotherapy efficacy and predict patient outcomes.

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