title: FoxO3 suppresses Myc-driven lymphomagenesis.
abstract: This study demonstrates, for the first time, that loss of a single forkhead box class O (FoxO) transcription factor, can promote lymphomagenesis. Using two different mouse models, we show that FoxO3 has a significant tumour-suppressor function in the context of Myc-driven lymphomagenesis. Loss of FoxO3 significantly accelerated myeloid tumorigenesis in vavP-MYC10 transgenic mice and B lymphomagenesis in Eμ-myc transgenic mice. Tumour analysis indicated that the selective pressure for mutation of the p53 pathway during Eμ-myc lymphomagenesis was not altered. Frank tumours were preceded by elevated macrophage numbers in FoxO3(-/-) vavP-MYC10 mice but, surprisingly, pre-B-cell numbers were relatively normal in healthy young FoxO3(-/-)Eμ-myc mice. In vitro assays revealed enhanced survival capacity of Myc-driven cells lacking FoxO3, but no change in cell cycling was detected. The loss of FoxO3 may also be affecting other tumour-suppressive functions for which FoxO1/4 cannot fully compensate.
authors.affiliation: Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Vandenberg
authors.affiliation: Department of Human Nutrition, Sugiyama Jogakuen University School of Life Studies, Chikusa-ku, Nagoya, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Motoyama
authors.affiliation: Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Cory
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc