Notch3 negatively regulates chemoresistance in breast cancers
| Autor: | Chunxiao Lu, Xin Ma, De-Quan Liu, Yangfan Lu, Dongxu He, Xiao-Ting Gu, Jian Jin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Chemotherapy Transition (genetics) Anthracycline business.industry medicine.medical_treatment Notch signaling pathway General Medicine medicine.disease 03 medical and health sciences 030104 developmental biology Breast cancer Antigen Internal medicine Cancer cell Medicine Signal transduction business |
| Zdroj: | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. |
| ISSN: | 1423-0380 |
| Popis: | To define the role of the NOTCH signaling pathway in the development of chemoresistance and the associated epithelial-mesenchymal transition (EMT), we investigated the effect of Notch3 on adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM cells). We found that Notch3 was downregulated and involved in the chemoresistance of MCF-7/ADM cells, while forced expression of Notch3 reversed the chemoresistance. Furthermore, fos-related antigen 1 (Fra1) was negatively regulated by Notch3 and was highly expressed in MCF-7/ADM cells. Increased Fra1 activated the EMT process. Finally, Notch3 expression was confirmed in clinically chemoresistant samples of breast cancers from patients receiving anthracycline-based chemotherapy. Low expression of Notch3 was an unfavorable predictor of distant relapse-free survival in ER positive breast cancers. Taken together, our findings demonstrate that the Notch3-Fra1 signaling pathway mediates chemoresistance via the EMT. |
| Databáze: | OpenAIRE |
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