MUC1 induces tamoxifen resistance in estrogen receptor-positive breast cancer

• Published in: Expert review of anticancer therapy Vol. 17; no. 7; pp. 607 - 613
• Main Authors: Merikhian, Parnaz, Ghadirian, Reyhane, Farahmand, Leila, Mansouri, Sepideh, Majidzadeh-A, Keivan
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-07-2017
• Subjects: Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - pharmacology; Apoptosis - drug effects; Breast Cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; cancer progression; Drug Resistance, Neoplasm - genetics; estrogen receptor; Female; Gene Expression Regulation, Neoplastic; Humans; MUC1-C; Mucin; Mucin-1 - genetics; Receptors, Estrogen - metabolism; Signal Transduction - drug effects; signaling pathways; Tamoxifen - administration & dosage; Tamoxifen - pharmacology; Tamoxifen resistance development; Mucin; signaling pathways; cancer progression; estrogen receptor; Tamoxifen resistance development; Breast Cancer; MUC1-C
• ISSN: 1473-7140; 1744-8328
• DOI: 10.1080/14737140.2017.1340837

Introduction: Tamoxifen, as an essential therapeutic tool in the treatment of estrogen receptor-positive breast cancer, has been available for the past three decades and is currently being utilized as a chemo-preventive agent for patients at high risk for breast carcinoma. However, the induction of chemo-resistance during therapy has indicated a significant challenge with regards to this agent.
Areas covered: This review enumerates the role of MUC1-C proto-oncogene in tamoxifen resistance and describes a number of signaling pathways by which MUC1-C would mediate the development of resistance. Finally, recent clinical studies conducted on the magnitude of MUC1 in inducing tamoxifen resistance are described.
Expert commentary: Mucin 1, or MUC1, is aberrantly overexpressed on the entire tumor cell surface of most human cancers. Thus, it may result in the upregulation of several signaling pathways, such as growth cascades related to receptor tyrosine kinases (RTK), β-catenin and E-cadherin, as well as promoting gene transcription of Ras-related protein Rab-31 in order to mediate tumor growth control in response to tamoxifen. On the contrary, MUC1 suppresses apoptotic events, which in turn impresses upon cell fate. Also, it has been demonstrated that silencing MUC1-C proto-oncogene is associated with increased sensitivity to tamoxifen-induced growth inhibitors.