Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/67536
Registo completo
Campo DC | Valor | Idioma |
---|---|---|
dc.contributor.author | Costa, Bruno Marques | por |
dc.contributor.author | Smith, Justin S. | por |
dc.contributor.author | Chen, Ying | por |
dc.contributor.author | Chen, Justin | por |
dc.contributor.author | Phillips, Heidi S. | por |
dc.contributor.author | Aldape, Kenneth D. | por |
dc.contributor.author | Zardo, Giuseppe | por |
dc.contributor.author | Nigro, Janice | por |
dc.contributor.author | James, C. David | por |
dc.contributor.author | Fridlyand, Jane | por |
dc.contributor.author | Reis, R. M. | por |
dc.contributor.author | Costello, Joseph F. | por |
dc.date.accessioned | 2020-10-16T14:02:09Z | - |
dc.date.available | 2020-10-16T14:02:09Z | - |
dc.date.issued | 2010-01 | - |
dc.identifier.citation | Costa, B. M., Smith, J. S., Chen, Y., Chen, J., et. al. (2010). Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma. Cancer research, 70(2), 453-462 | por |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://hdl.handle.net/1822/67536 | - |
dc.description.abstract | HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using reverse transcription-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrently activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a phosphoinostide 3-kinase (PI3K) inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with tumor necrosis factor-related apoptosis-including ligand resistance. Notably, aberrant expression of HOXA9 was independently predictive of shorter overall and progression-free survival in two GBM patient sets and improved survival prediction by MGMT promoter methylation. Thus, HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Our findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression with implications for mTOR or PI3K targeted therapies. | por |
dc.description.sponsorship | NIH grants NIH CA094971 (J.F. Costello) and NIH/NCI F32 CA113039-01 (J.S. Smith); Karen Osney Brownstein Endowed Chair (J.F. Costello); UC Discovery grant Bio05-10501 (J.F. Costello and H.S. Phillips); Portuguese Science and Technology Foundation SFRH/BD/15258/2004 (B.M. Costa); and Luso-American Development Foundation, Portugal 186/06 (B.M. Costa) | por |
dc.language.iso | eng | por |
dc.publisher | American Association for Cancer Research | por |
dc.rights | openAccess | por |
dc.subject | Adult | por |
dc.subject | Apoptosis | por |
dc.subject | Astrocytoma | por |
dc.subject | Brain Neoplasms | por |
dc.subject | Cell Growth Processes | por |
dc.subject | DNA Modification Methylases | por |
dc.subject | DNA Repair Enzymes | por |
dc.subject | Disease-Free Survival | por |
dc.subject | Epigenesis, Genetic | por |
dc.subject | Glioblastoma | por |
dc.subject | Histones | por |
dc.subject | Homeodomain Proteins | por |
dc.subject | Humans | por |
dc.subject | Phosphatidylinositol 3-Kinases | por |
dc.subject | Promoter Regions, Genetic | por |
dc.subject | Survival Rate | por |
dc.subject | Transcriptional Activation | por |
dc.subject | Tumor Suppressor Proteins | por |
dc.subject | Gene Expression Regulation, Neoplastic | por |
dc.subject | Phosphoinositide-3 Kinase Inhibitors | por |
dc.title | Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://cancerres.aacrjournals.org/content/70/2/453.short | por |
oaire.citationStartPage | 453 | por |
oaire.citationEndPage | 462 | por |
oaire.citationIssue | 2 | por |
oaire.citationVolume | 70 | por |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-09-2189 | por |
dc.identifier.pmid | 20068170 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Cancer Research | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Costa-2010-Reversing-hoxa-oncogene-activation-.pdf | 472,31 kB | Adobe PDF | Ver/Abrir |