Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor suppression in vivo.
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.
Dansen
Tobias B
TB
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.
Whitfield
Jonathan
J
Rostker
Fanya
F
Brown-Swigart
Lamorna
L
Evan
Gerard I
GI
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*
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