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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: 3' Untranslated Regions, Adult, Aged, Ataxia Telangiectasia Mutated Proteins, Blotting, Western, Breast Neoplasms, Combined Modality Therapy, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, In Situ Hybridization, MicroRNAs, Middle Aged, Neoplasm Recurrence, Local, Prognosis, RNA, Small Interfering, Tumor Cells, Cultured.
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Does estrogen receptor α regulate ATM Expression through miRNAs in breast cancer? Context: Estrogen receptor α (ERα) is an essential element regulating mammary gland development and it contributes to breast cancer development and progression. Most of the ER-negative breast cancers display more aggressive clinical behaviors and are resistant to antiestrogen therapies. In addition, many ER-negative tumors show insensitivity to many chemotherapeutic drugs and radiotherapy, although mechanisms underlying this phenotype are less clear. We conducted immunohistochemistry on 296 cases of breast cancer tissues using a variety of antibodies. On the basis of the clinical data, we conducted siRNA knockdown to study the role of ERα on ATM expression in breast cancer cell lines. Furthermore, we used antisense oligonucleotides against micro RNAs (miRNA) or miRNA overexpression plasmids to study the role of miR-18a and -106a on ATM expression. Finally we used in situ hybridization to assess miR-18a and -106a expression in breast cancer tissues. We found that in ER-negative breast cancer tissues, expression of the ATM kinase, a critical DNA damage-response protein, is aberrantly upregulated. We also found that the locoregional recurrence rate after radiotherapy positively correlates with ATM expression. On the cellular level, we showed that ERα, but not ERβ, negatively regulates ATM expression. Furthermore, we identified that ERα activates miR-18a and -106a to downregulate ATM expression. We also showed that miR-18a and -106a were significantly underexpressed in ER-negative breast cancer tissues.
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We reveal a novel mechanism involving ERα and miR-18a and -106a regulation of ATM in breast cancer. Final Decision: yes