title: Src family kinases promote AML cell survival through activation of signal transducers and activators of transcription (STAT).
abstract: We investigated the role of Src family kinases (SFKs) in the regulation of STAT activation in myeloid leukemia cells. Two of 6 AML cell lines displayed constitutive STAT5 activation, whereas four cell lines had constitutive SFK activity. Treatment with the SFK inhibitors suppressed STAT5 activation and decreased viability. Akt phosphorylation and Mcl-1 expression decreased after SFK inhibition accompanied by apoptosis induction. In primary AML specimens, SFK inhibitors suppressed proliferation in 5 of 14 specimens. These data indicate that Src-STAT5 and Src-Akt pathways are integral survival signal pathways in AML cells. Src inhibition may represent a novel treatment strategy for investigation in AML.
authors.affiliation: Experimental Therapeutics, H. Lee Moffitt Cancer & Research Institute, Tampa, FL 33612, United States. ozaway@med.nagoya-u.ac.jp
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Ann H
authors.initials: AH
authors.lastname: Williams
authors.forename: Myka L
authors.initials: ML
authors.lastname: Estes
authors.forename: Norimasa
authors.initials: N
authors.lastname: Matsushita
authors.forename: Frank
authors.initials: F
authors.lastname: Boschelli
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050791:STAT Transcription Factors; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt