RhoC upregulation is correlated with reduced E-cadherin in human breast cancer specimens after chemotherapy and in human breast cancer MCF-7 cells
| Autor: | Tomoko Kamiakito, Hirotoshi Kawata, Yawara Omoto, C. Miyazaki, Yasuo Hozumi, Akira Tanaka |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult rho GTP-Binding Proteins Cancer Research medicine.medical_specialty Epithelial-Mesenchymal Transition Endocrinology Diabetes and Metabolism RhoC Down-Regulation Breast Neoplasms Prostate cancer Endocrinology Breast cancer Internal medicine Biomarkers Tumor Medicine Humans Epithelial–mesenchymal transition Aged Etoposide Neoplasm Staging Aged 80 and over biology Endocrine and Autonomic Systems business.industry Cancer Middle Aged medicine.disease Cadherins Antineoplastic Agents Phytogenic Fibronectins Up-Regulation Gene Expression Regulation Neoplastic Actin Cytoskeleton MCF-7 Drug Resistance Neoplasm rhoC GTP-Binding Protein Cancer cell biology.protein MCF-7 Cells Female business RhoC GTP-Binding Protein |
| Zdroj: | Hormonescancer. 5(6) |
| ISSN: | 1868-8500 |
| Popis: | Therapy-resistant cancer cells are a major problem in cancer research. Recent studies suggest that the epithelial-mesenchymal transition (EMT) is a key mechanism in therapy resistance. Yet, the expressions of EMT markers, EMT core regulators, and a stem cell marker of BMI1 during chemotherapy have been poorly analyzed in clinical breast cancer specimens. In the present study, we investigated the roles of RhoC under chemotherapy to follow up on earlier findings demonstrating the involvement of RhoC in prostate cancer resistance to endocrine therapy. Immunohistochemically, E-cadherin expression was significantly lower in human breast cancer specimens analyzed after chemotherapy than specimens biopsied before chemotherapy. Significant upregulation of fibronectin, a mesenchymal EMT marker, was found in post-chemotherapy analysis. A study of the EMT core regulators of SNAIL1, SNAIL2, TWIST1, and a well-known stem cell marker of BMI1 revealed no post-chemotherapy upregulation of these molecules. In contrast, RhoC expression was significantly upregulated in post-chemotherapy breast cancer specimens. MCF-7 cells stably transfected with the constitutive active (CA) RhoC plasmid manifested a reduced level of E-cadherin at the peripheries and disorganization of actin fibers, with no accompanying upregulation of SNAIL1, SNAIL2, TWIST1, or BMI1 in Western blots. Exposure of etoposide on MCF-7 cells showed RhoC upregulation together with reduced membranous expression of E-cadherin and disorganization of actin fibers. In MTT assay, however, the CA-RhoC-expressing MCF-7 cells failed to show chemotherapy resistance under etoposide treatment. Taken in sum, RhoC may contribute to an EMT-like process in human breast cancer during chemotherapy. |
| Databáze: | OpenAIRE |
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