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Progress in the Understanding of Estrogen Receptor Alpha Signaling in Triple-Negative Breast Cancer: Reactivation of Silenced ER-α and Signaling through ER-α36.
Al-Kabariti, Aya Y; Abbas, Manal A.
Afiliação
  • Al-Kabariti AY; Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
  • Abbas MA; Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University, Amman, Jordan.
Mol Cancer Res ; 21(11): 1123-1138, 2023 11 01.
Article em En | MEDLINE | ID: mdl-37462782
Triple-negative breast cancer (TNBC) is an aggressive tumor that accounts for approximately 15% of total breast cancer cases. It is characterized by poor prognosis and high rate of recurrence compared to other types of breast cancer. TNBC has a limited range of treatment options that include chemotherapy, surgery, and radiation due to the absence of estrogen receptor alpha (ER-α) rendering hormonal therapy ineffective. However, possible targets for improving the clinical outcomes in TNBC exist, such as targeting estrogen signaling through membranous ER-α36 and reactivating silenced ER-α. It has been shown that epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can restore the expression of ER-α. This reactivation of ER-α, presents a potential strategy to re-sensitize TNBC to hormonal therapy. Also, this review provides up-to-date information related to the direct involvement of miRNA in regulating the translation of ER-α mRNA. Specific epi-miRNAs can regulate ER-α expression indirectly by post-transcriptional targeting of mRNAs of enzymes that are involved in DNA methylation and histone deacetylation. Furthermore, ER-α36, an alternative splice variant of ER-α66, is highly expressed in ER-negative breast tumors and activates MAPK/ERK pathway, promoting cell proliferation, escaping apoptosis, and enhancing metastasis. In the future, these recent advances may be helpful for researchers working in the field to obtain novel treatment options for TNBC, utilizing epigenetic drugs and epi-miRNAs that regulate ER-α expression. Also, there is some evidence to suggest that drugs that decrease the expression of ER-α36 may be effective in treating TNBC.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / MicroRNAs / Neoplasias de Mama Triplo Negativas Limite: Female / Humans Idioma: En Revista: Mol Cancer Res Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Jordânia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / MicroRNAs / Neoplasias de Mama Triplo Negativas Limite: Female / Humans Idioma: En Revista: Mol Cancer Res Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Jordânia