Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance. (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Alternative label

• McCubrey JA, Abrams SL, Ligresti G, Misaghian N, Wong EW, Steelman LS, Bäsecke J, Troppmair J, Libra M, Nicoletti F, Molton S, McMahon M, Evangelisti C, Martelli AM. (2008)
  Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance.
  in Leukemia
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• McCubrey JA, Abrams SL, Ligresti G, Misaghian N, Wong EW, Steelman LS, Bäsecke J, Troppmair J, Libra M, Nicoletti F, Molton S, McMahon M, Evangelisti C, Martelli AM. (literal)

Pagina inizio

• 2080 (literal)

Pagina fine

• 2090 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 22 (literal)

Rivista

• Leukemia (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA; Department of Biomedical Sciences, Section of Clinical Pathology and Molecular Oncology, University of Catania, Catania, Italy; Division of Hematology and Oncology, Department of Medicine, University of Göttingen, Göttingen, Germany; Daniel-Swarovski-Research Laboratory, Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Cellular and Molecular Pharmacology, Cancer Research Institute, University of California-San Francisco, San Francisco, CA, USA; Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy; IGM/C.N.R., c/o I.O.R., Bologna, Italy (literal)

Titolo

• Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance. (literal)

Abstract

• A cytokine-dependent (FL5.12), drug-sensitive, p53 wild type (WT) and a doxorubicin-resistant derivative line (FL/Doxo) were used to determine the mechanisms that could result in drug resistance of early hematopoietic precursor cells. Drug resistance was associated with decreased p53 induction after doxorubicin treatment, which was due to a higher level of proteasomal degradation of p53. Dominant-negative (DN) p53 genes increased the resistance to chemotherapeutic drugs, MDM-2 and MEK inhibitors, further substantiating the role of p53 in therapeutic sensitivity. The involvement of signal transduction and apoptotic pathways was examined, as drug resistance did not appear to be due to increased drug efflux. Drug-resistant FL/Doxo cells had higher levels of activated Raf/MEK/ERK signaling and decreased induction of apoptosis when cultured in the presence of doxorubicin than drug-sensitive FL5.12 cells. Introduction of DN MEK1 increased drug sensitivity, whereas constitutively active (CA) MEK1 or conditionally active BRAF augmented resistance, documenting the importance of the Raf/MEK/ERK pathway in drug resistance. MEK inhibitors synergized with chemotherapeutic drugs to reduce the IC(50). Thus the p53 and Raf/MEK/ERK pathways play key roles in drug sensitivity. Targeting these pathways may be effective in certain drug-resistant leukemias that are WT at p53.Leukemia (2008) 22, 2080-2090; doi:10.1038/leu.2008.207; published online 7 August 2008 (literal)

Prodotto di

• Bersagli molecolari per il controllo della progressione tumorale (ME.P03.012.001) (Modulo)
• Institute of molecular genetics (IGM) (Istituto)

Autore CNR

• Alberto Maria Martelli (Unità di personale esterno)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Bersagli molecolari per il controllo della progressione tumorale (ME.P03.012.001) (Modulo)

Autore CNR di

• Alberto Maria Martelli (Unità di personale esterno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Leukemia (Rivista)