Figure 4.

Luciferase imaging of SCLC in chimeras.

1. In vivo imaging of a invCAG-Luc;Rb1^F/F ;Trp53^F/F chimeric mouse injected intrathoracically with Ad5-Cre. Tumor growth was monitored weekly by bioluminescence imaging.
2. Luciferase activity emitted from the thorax of 10 chimeric invCAG-Luc;Rb1^F/F ;Trp53^F/F mice. Each line represents measurements of an individual mouse. The chimeric mouse with the lowest coat-color chimerism (○, 20%) did not develop a tumor, while the second lowest chimera (□, 35%) did develop SCLC though with a long latency. One chimera (♦, 962975) failed to show any Luciferase activity but did develop SCLC. Analysis of the tumor revealed a lack of Cre-mediated switching of the invCag-Luc transgene (supplementary Fig S7).
3. Survival curves of chimeric Rb1^F/F ;Trp53^F/F mice containing either the invCag-Luc (black line) or the invCag-MycL1-Luc (red line) transgene, intratracheally injected with Ad5-Cre. Median survival indicated by the dotted line was 250 and 167 days, respectively.
4. Survival curves of F1 Rb1^F/F ;Trp53^F/F mice containing either the invCag-Luc (black line) or the invCag-MycL1-Luc (red line) transgene, intratracheally injected with Ad5-Cre. Median survival indicated by the dotted line was 235 and 140 days, respectively.
5. Luciferase activity emitted from the thorax of 11 F1 invCAG-MycL1-Luc;Rb1^F/F ;Trp53^F/F mice. Each line represents measurements of an individual mouse.
6. MycL1 copy number in SCLC tumors from three different genotypes determined by real-time PCR and aCGH. Each circle represents a primary SCLC tumor. All tumors with more than four copies (dotted line) were considered positive for MycL1 amplification. Note that overexpression of MycL1 by the transgene significantly reduces the frequency of genomic MycL1 amplifications in tumors as compared to the Rb1^F/F ;Trp53^F/F control ( P = 0.002 Fisher's Exact Test) and the invCAG-Luc;Rb1^F/F ;Trp53^F/F control ( P = 0.035 Fischer's Exact Test).