title: Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor suppression in vivo.
abstract: Bax and Bak comprise the mitochondrial gateway for apoptosis induced by diverse stimuli. Loss of both bax and bak is necessary to block cell death induced by such stimuli, indicating a great degree of functional overlap between Bax and Bak. Apoptosis is the major intrinsic pathway that limits the oncogenic potential of Myc. Using a switchable mouse model of Myc-induced apoptosis in pancreatic beta cells, we have shown that Myc induces apoptosis in vivo exclusively through Bax but not Bak. Furthermore, blockade of Myc-induced apoptosis by the inactivation of Bax, but not Bak, eliminates all restraints to the oncogenic potential of Myc, allowing the rapid and synchronous progression of invasive, angiogenic tumors.
authors.affiliation: Cancer Research Institute and Department of Cellular and Molecular Pharmacology, Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-0875, USA.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Dansen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Whitfield
authors.forename: Fanya
authors.initials: F
authors.lastname: Rostker
authors.forename: Lamorna
authors.initials: L
authors.lastname: Brown-Swigart
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005934:Glucagon / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010179:Pancreas / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D016271:Proto-Oncogene Proteins c-myc; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D013629:Tamoxifen; D005934:Glucagon