ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.18632/oncotarget.14295 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/19542 |
Resumo: | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil |
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Lucena-Araujo, Antonio R.Coelho-Silva, Juan L.Pereira-Martins, Diego A.Thomé, CarolinaScheucher, Priscila S.Lange, Ana P.Paiva, Helder H.Hemmelgarn, Benjamin T.Morais-Sobral, Mariana C.Azevedo, Elisa A.Franca-Neto, Pedro L.Franca, Rafael F.Silva, Cleide L.Krause, AlexandreRego, Eduardo M.2017-06-27T19:06:05Z2017-06-27T19:06:05Z2017LUCENA-ARAUJO, A. R. et al. ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype. Oncotarget, v. 8, n. 5, p. 8475–8483, 31 jan. 2017. DOI 10.18632/oncotarget.14295.1949-2553https://www.arca.fiocruz.br/handle/icict/1954210.18632/oncotarget.14295porProteína Tumoral p73Isoformas de ProteínaLeucemia Promielocítica Agudaacute promyelocytic leukemiaΔNp73apoptosisbone marrow transplantationlentiviral gene transferProteína Tumoral p73Isoformas de ProteínaLeucemia Promielocítica AgudaApoptoseTransplante de Medula ÓsseaΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotypeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, BrasilHere, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis. Next, we evaluated the effect of ΔNp73 on stem-cell self-renewal and myeloid differentiation. Primary BM cells lentivirally infected with human ΔNp73 were not immortalized in culture and did not present significant changes in the percentage of CD11b. Finally, we assessed the impact of ΔNp73 on leukemogenesis or its possible cooperation with PML/RARA fusion protein in the induction of an APL-leukemic phenotype. After 120 days of follow-up, all transplanted mice were clinically healthy and, no evidence of leukemia/myelodysplasia was apparent. Taken together, our data suggest that ΔNp73 had no leukemic transformation capacity by itself and apparently did not cooperate with the PML/RARA fusion protein to induce a leukemic phenotype in a murine BM transplantation model. In addition, the forced expression of ΔNp73 in murine BM progenitors did not alter the ATRA-induced differentiation rate in vitro or induce aberrant cell proliferation, but exerted an important role in cell survival, providing resistance to drug-induced apoptosis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/19542/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINAL28035072 2017 luc-del.oa.pdf28035072 2017 luc-del.oa.pdfapplication/pdf4478429https://www.arca.fiocruz.br/bitstream/icict/19542/2/28035072%202017%20luc-del.oa.pdf61bc5d712c23456202844fe304767446MD52TEXT28035072 2017 luc-del.oa.pdf.txt28035072 2017 luc-del.oa.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| title |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| spellingShingle |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype Lucena-Araujo, Antonio R. Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda acute promyelocytic leukemia ΔNp73 apoptosis bone marrow transplantation lentiviral gene transfer Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda Apoptose Transplante de Medula Óssea |
| title_short |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| title_full |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| title_fullStr |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| title_full_unstemmed |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| title_sort |
ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype |
| author |
Lucena-Araujo, Antonio R. |
| author_facet |
Lucena-Araujo, Antonio R. Coelho-Silva, Juan L. Pereira-Martins, Diego A. Thomé, Carolina Scheucher, Priscila S. Lange, Ana P. Paiva, Helder H. Hemmelgarn, Benjamin T. Morais-Sobral, Mariana C. Azevedo, Elisa A. Franca-Neto, Pedro L. Franca, Rafael F. Silva, Cleide L. Krause, Alexandre Rego, Eduardo M. |
| author_role |
author |
| author2 |
Coelho-Silva, Juan L. Pereira-Martins, Diego A. Thomé, Carolina Scheucher, Priscila S. Lange, Ana P. Paiva, Helder H. Hemmelgarn, Benjamin T. Morais-Sobral, Mariana C. Azevedo, Elisa A. Franca-Neto, Pedro L. Franca, Rafael F. Silva, Cleide L. Krause, Alexandre Rego, Eduardo M. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Lucena-Araujo, Antonio R. Coelho-Silva, Juan L. Pereira-Martins, Diego A. Thomé, Carolina Scheucher, Priscila S. Lange, Ana P. Paiva, Helder H. Hemmelgarn, Benjamin T. Morais-Sobral, Mariana C. Azevedo, Elisa A. Franca-Neto, Pedro L. Franca, Rafael F. Silva, Cleide L. Krause, Alexandre Rego, Eduardo M. |
| dc.subject.other.pt_BR.fl_str_mv |
Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda |
| topic |
Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda acute promyelocytic leukemia ΔNp73 apoptosis bone marrow transplantation lentiviral gene transfer Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda Apoptose Transplante de Medula Óssea |
| dc.subject.en.pt_BR.fl_str_mv |
acute promyelocytic leukemia ΔNp73 apoptosis bone marrow transplantation lentiviral gene transfer |
| dc.subject.decs.pt_BR.fl_str_mv |
Proteína Tumoral p73 Isoformas de Proteína Leucemia Promielocítica Aguda Apoptose Transplante de Medula Óssea |
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Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil |
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2017 |
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2017-06-27T19:06:05Z |
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2017-06-27T19:06:05Z |
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2017 |
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LUCENA-ARAUJO, A. R. et al. ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype. Oncotarget, v. 8, n. 5, p. 8475–8483, 31 jan. 2017. DOI 10.18632/oncotarget.14295. |
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1949-2553 |
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10.18632/oncotarget.14295 |
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LUCENA-ARAUJO, A. R. et al. ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype. Oncotarget, v. 8, n. 5, p. 8475–8483, 31 jan. 2017. DOI 10.18632/oncotarget.14295. 1949-2553 10.18632/oncotarget.14295 |
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