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Trabectedin (ET-743...
Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors.
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Forni, Claudia (författare)
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Minuzzo, Mario (författare)
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Virdis, Emanuela (författare)
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Tamborini, Elena (författare)
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Simone, Matteo (författare)
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Tavecchio, Michele (författare)
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Erba, Eugenio (författare)
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Grosso, Federica (författare)
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Gronchi, Alessandro (författare)
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- Åman, Pierre, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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Casali, Paolo (författare)
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D'Incalci, Maurizio (författare)
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Pilotti, Silvana (författare)
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Mantovani, Roberto (författare)
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(creator_code:org_t)
- 2009
- 2009
- Engelska.
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Ingår i: Molecular cancer therapeutics. - 1535-7163. ; 8:2, s. 449-57
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Differentiation is a complex set of events that can be blocked by rearrangements of regulatory genes producing fusion proteins with altered properties. In the case of myxoid liposarcoma (MLS) tumors, the causative abnormality is a fusion between the CHOP transcription factor and the FUS or EWS genes. CHOP belongs to and is a negative regulator of the large CAAT/enhancer binding protein family whose alpha, beta, and delta members are master genes of adipogenesis. Recent clinical data indicate a peculiar sensitivity of these tumors to the natural marine compound trabectedin. One hypothesis is that the activity of trabectedin is related to the inactivation of the FUS-CHOP oncogene. We find that trabectedin causes detachment of the FUS-CHOP chimera from targeted promoters. Reverse transcription-PCR and chromatin immunoprecipitation analysis in a MLS line and surgical specimens of MLS patients in vivo show activation of the CAAT/enhancer binding protein-mediated transcriptional program that leads to morphologic changes of terminal adipogenesis. The activity is observed in cells with type 1 but not type 8 fusions. Hence, the drug induces maturation of MLS lipoblasts in vivo by targeting the FUS-CHOP-mediated transcriptional block. These data provide a rationale for the specific activity of trabectedin and open the perspective of combinatorial treatments with drugs acting on lipogenic pathways.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Adipogenesis
- drug effects
- genetics
- Antineoplastic Agents
- pharmacology
- Apoptosis
- drug effects
- CCAAT-Enhancer-Binding Protein-beta
- metabolism
- Cell Differentiation
- drug effects
- Cell Line
- Tumor
- Dioxoles
- pharmacology
- Drug Screening Assays
- Antitumor
- Female
- Gene Expression Regulation
- Neoplastic
- drug effects
- Humans
- Liposarcoma
- Myxoid
- genetics
- pathology
- Male
- Middle Aged
- Oncogene Proteins
- Fusion
- genetics
- Protein Binding
- drug effects
- RNA-Binding Protein FUS
- genetics
- Tetrahydroisoquinolines
- pharmacology
- Transcription Factor CHOP
- genetics
- Tumor Markers
- Biological
- metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Forni, Claudia
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Minuzzo, Mario
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Virdis, Emanuela
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Tamborini, Elena
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Simone, Matteo
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Tavecchio, Miche ...
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visa fler...
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Erba, Eugenio
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Grosso, Federica
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Gronchi, Alessan ...
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Åman, Pierre, 19 ...
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Casali, Paolo
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D'Incalci, Mauri ...
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Pilotti, Silvana
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Mantovani, Rober ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kirurgi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Molecular cancer ...
- Av lärosätet
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Göteborgs universitet