Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines

• Published in: PloS one 2011-11, Vol.6 (11), p.e27707
• Main Authors: de Carvalho, Fabricio, Costa, Erico T, Camargo, Anamaria A, Gregorio, Juliana C, Masotti, Cibele, Andrade, Valeria C C, Strauss, Bryan E, Caballero, Otavia L, Atanackovic, Djordje, Colleoni, Gisele W B
• Format: Article
• Language: English
• Subjects: Adenoviruses; Analysis; Annexin V; Antigens; Antigens, Neoplasm - genetics; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Biology; Bone marrow; Boronic Acids - pharmacology; Bortezomib; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cell Division - drug effects; Cell Division - genetics; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA synthesis; G2 Phase - drug effects; G2 Phase - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Gene Silencing; Gene therapy; Genetic research; Genomics; Growth factors; Humans; Immunotherapy; Laboratories; Medical prognosis; Medical research; Medicine; Molecular biology; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Neoplasm Invasiveness; Neoplasm Proteins - deficiency; Neoplasm Proteins - genetics; Ovarian cancer; Plasma cells; Protease Inhibitors - pharmacology; Proteasome Inhibitors; Pyrazines - pharmacology; R&D; Reduction; Research & development; RNA, Small Interfering - genetics; Tumor cell lines; Tumorigenesis; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027707

The MAGE-C1/CT7 encodes a cancer/testis antigen (CTA), is located on the chromosomal region Xq26-27 and is highly polymorphic in humans. MAGE-C1/CT7 is frequently expressed in multiple myeloma (MM) that may be a potential target for immunotherapy in this still incurable disease. MAGEC1/CT7 expression is restricted to malignant plasma cells and it has been suggested that MAGE-C1/CT7 might play a pathogenic role in MM; however, the exact function this protein in the pathophysiology of MM is not yet understood. Our objectives were (1) to clarify the role of MAGE-C1/CT7 in the control of cellular proliferation and cell cycle in myeloma and (2) to evaluate the impact of silencing MAGE-C1/CT7 on myeloma cells treated with bortezomib. Myeloma cell line SKO-007 was transduced for stable expression of shRNA-MAGE-C1/CT7. Downregulation of MAGE-C1/CT7 was confirmed by real time quantitative PCR and western blot. Functional assays included cell proliferation, cell invasion, cell cycle analysis and apoptosis. Western blot showed a 70-80% decrease in MAGE-C1/CT7 protein expression in inhibited cells (shRNA-MAGE-C1/CT7) when compared with controls. Functional assays did not indicate a difference in cell proliferation and DNA synthesis when inhibited cells were compared with controls. However, we found a decreased percentage of cells in the G2/M phase of the cell cycle among inhibited cells, but not in the controls (p