Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines.
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 expressio...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/c5b75998a15e4ceb80f81b61485aeab2 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:c5b75998a15e4ceb80f81b61485aeab2 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:c5b75998a15e4ceb80f81b61485aeab22021-11-18T07:34:07ZTargeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines.1932-620310.1371/journal.pone.0027707https://doaj.org/article/c5b75998a15e4ceb80f81b61485aeab22011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110734/?tool=EBIhttps://doaj.org/toc/1932-6203The 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<0.05). When myeloma cells were treated with bortezomib, we observed a 48% reduction of cells in the G2/M phase among inhibited cells while controls showed 13% (empty vector) and 9% (ineffective shRNA) reduction, respectively (p<0.01). Furthermore, inhibited cells treated with bortezomib showed an increased percentage of apoptotic cells (Annexin V+/PI-) in comparison with bortezomib-treated controls (p<0.001). We found that MAGE-C1/CT7 protects SKO-007 cells against bortezomib-induced apoptosis. Therefore, we could speculate that MAGE-C1/CT7 gene therapy could be a strategy for future therapies in MM, in particular in combination with proteasome inhibitors.Fabricio de CarvalhoErico T CostaAnamaria A CamargoJuliana C GregorioCibele MasottiValeria C C AndradeBryan E StraussOtavia L CaballeroDjordje AtanackovicGisele W B ColleoniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27707 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Fabricio de Carvalho Erico T Costa Anamaria A Camargo Juliana C Gregorio Cibele Masotti Valeria C C Andrade Bryan E Strauss Otavia L Caballero Djordje Atanackovic Gisele W B Colleoni Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| description |
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<0.05). When myeloma cells were treated with bortezomib, we observed a 48% reduction of cells in the G2/M phase among inhibited cells while controls showed 13% (empty vector) and 9% (ineffective shRNA) reduction, respectively (p<0.01). Furthermore, inhibited cells treated with bortezomib showed an increased percentage of apoptotic cells (Annexin V+/PI-) in comparison with bortezomib-treated controls (p<0.001). We found that MAGE-C1/CT7 protects SKO-007 cells against bortezomib-induced apoptosis. Therefore, we could speculate that MAGE-C1/CT7 gene therapy could be a strategy for future therapies in MM, in particular in combination with proteasome inhibitors. |
| format |
article |
| author |
Fabricio de Carvalho Erico T Costa Anamaria A Camargo Juliana C Gregorio Cibele Masotti Valeria C C Andrade Bryan E Strauss Otavia L Caballero Djordje Atanackovic Gisele W B Colleoni |
| author_facet |
Fabricio de Carvalho Erico T Costa Anamaria A Camargo Juliana C Gregorio Cibele Masotti Valeria C C Andrade Bryan E Strauss Otavia L Caballero Djordje Atanackovic Gisele W B Colleoni |
| author_sort |
Fabricio de Carvalho |
| title |
Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| title_short |
Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| title_full |
Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| title_fullStr |
Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| title_full_unstemmed |
Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| title_sort |
targeting mage-c1/ct7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/c5b75998a15e4ceb80f81b61485aeab2 |
| work_keys_str_mv |
AT fabriciodecarvalho targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT ericotcosta targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT anamariaacamargo targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT julianacgregorio targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT cibelemasotti targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT valeriaccandrade targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT bryanestrauss targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT otavialcaballero targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT djordjeatanackovic targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines AT giselewbcolleoni targetingmagec1ct7expressionincreasescellsensitivitytotheproteasomeinhibitorbortezomibinmultiplemyelomacelllines |
| _version_ |
1718423312211640320 |