P53 status dictates responses of B lymphomas to monotherapy with proteasome inhibitors.

ABSTRACT: The proapoptotic function of p53 is thought to underlie most anticancer modalities and is also activated in response to oncogenic insults, such as overexpression of the Myc oncoprotein. Here we generated tractable B lymphomas using retroviral transduction of the MYC oncogene into hematopoietic cells with 2 knock-in alleles encoding a fusion between p53 and 4-hydroxytamoxifen (4OHT) receptor (p53ER(TAM)). In these polyclonal tumors, Myc is the only oncogenic lesion, and p53ER(TAM) status can be rapidly toggled between "off" and "on" with 4OHT, provided that the Trp53 promoter has been independently activated. Although 4OHT can trigger widespread apoptosis and overt tumor regression even in the absence of DNA-damaging agents, in tumors with high levels of Mdm2 these responses are blunted. Ho

SUBMITTER: Yu D 

PROVIDER: S-EPMC1885530 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature