[HTML][HTML] Suppression of Myc-induced apoptosis in β cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression

S Pelengaris, M Khan, GI Evan - Cell, 2002 - cell.com
S Pelengaris, M Khan, GI Evan
Cell, 2002cell.com
To explore the role of c-Myc in carcinogenesis, we have developed a reversible transgenic
model of pancreatic β cell oncogenesis using a switchable form of the c-Myc protein.
Activation of c-Myc in adult, mature β cells induces uniform β cell proliferation but is
accompanied by overwhelming apoptosis that rapidly erodes β cell mass. Thus, the
oncogenic potential of c-Myc in β cells is masked by apoptosis. Upon suppression of c-Myc-
induced β cell apoptosis by coexpression of Bcl-x L, c-Myc triggers rapid and uniform …
Abstract
To explore the role of c-Myc in carcinogenesis, we have developed a reversible transgenic model of pancreatic β cell oncogenesis using a switchable form of the c-Myc protein. Activation of c-Myc in adult, mature β cells induces uniform β cell proliferation but is accompanied by overwhelming apoptosis that rapidly erodes β cell mass. Thus, the oncogenic potential of c-Myc in β cells is masked by apoptosis. Upon suppression of c-Myc-induced β cell apoptosis by coexpression of Bcl-xL, c-Myc triggers rapid and uniform progression into angiogenic, invasive tumors. Subsequent c-Myc deactivation induces rapid regression associated with vascular degeneration and β 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.
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