Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression.
To explore the role of c-Myc in carcinogenesis, we have developed a reversible transgenic model of pancreatic beta cell oncogenesis using a switchable form of the c-Myc protein. Activation of c-Myc in adult, mature beta cells induces uniform beta cell proliferation but is accompanied by overwhelming apoptosis that rapidly erodes beta cell mass. Thus, the oncogenic potential of c-Myc in beta cells is masked by apoptosis. Upon suppression of c-Myc-induced beta cell apoptosis by coexpression of Bcl-x(L), c-Myc triggers rapid and uniform progression into angiogenic, invasive tumors. Subsequent c-Myc deactivation induces rapid regression associated with vascular degeneration and beta cell apoptosis. Our data indicate that highly complex neoplastic lesions can be both induced and maintained in vivo by a simple combination of two interlocking molecular lesions.
Pubmed ID: 12015982 RIS Download
3T3 Cells | Animals | Apoptosis | Cadherins | Cell Division | Cell Line | Cell Nucleus | Estrogen Antagonists | Genes, myc | Humans | Insulinoma | Islets of Langerhans | Mice | Mice, Inbred Strains | Mice, Transgenic | Mutation | Pancreatic Neoplasms | Promoter Regions, Genetic | Proto-Oncogene Proteins c-bcl-2 | Proto-Oncogene Proteins c-myc | Receptors, Estrogen | Tamoxifen | bcl-X Protein