Abstract B01: An allelic series of deregulated c-Myc expression interrogates the oncogenicity of distinct Myc levels in lung adenocarcinoma

A plethora of transgenic mouse models have found that c-Myc induces tumors inefficiently and requires cooperating mutations. Acute activation of high levels of Myc induces cellular proliferation, tempered by intrinsic tumor suppression via apoptosis. We hypothesized that low, near physiological, levels of deregulated Myc that fail to invoke tumor suppression pathways, would more effectively initiate sporadic tumors.We previously described the Rosa26lslMycER (R26MER) allele in which deregulated c-Myc is expressed at an endogenous-like level following expression of Cre-recombinase. This c-Myc is fused to a modified estrogen receptor, such that Myc function is dependent upon administration of tamoxifen. We have now generated a Rosa26CAGlslMycER (R26(C)MER) allele, in which the addition of the CAG enhancer has increased the amount of MycER driven by this locus 10-fold. Genetic combination of these alleles generates for the first time mice with tightly controlled and defined levels of switchable Myc protein.Lung cancer is the leading cause of cancer death worldwide and is commonly associated with elevated Myc levels. To determine the role of deregulated Myc expression in lung adenocarcinoma, intranasally administered Adenoviral Cre-recombinase was used to induce sporadic c-MycER expression at different levels in lung epithelial cells, and tamoxifen diet was used to activate c-MycER function. Whereas acute low levels of Myc induced proliferation, high levels of Myc induced both pro...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Modeling Myc in Mouse: Poster Presentations - Proffered Abstracts Source Type: research