Analysis of major signaling pathways in mouse <i>Kras/p53</i> tumors and marker expression in human lung cancer cell lines.

<p>(A) Quantitative PCR (qPCR) analysis of RNA extracted from tumors and adjacent non-tumor tissues derived from <i>SPC^CreER/+; p53^f/f; Kras^LSL-G12D/+</i> adult mice injected with tamoxifen. Target genes of each major signaling pathway were assessed for changes in their expression in tumor versus non-tumor tissues. The numbers represent fold of increase in tumor tissues. Multiple lung tumors from a single mouse and multiple mice were analyzed. <i>Ccnd1</i> (<i>cyclin D1</i>) was upregulated, consistent with increased Ki67 staining on tumor sections. Notch signaling was consistently upregulated in tumor versus non-tumor tissues whereas Platelet-derived growth factor (PDGF), Wnt, Bone morphogenetic protein (Bmp) and Hedgehog (Hh) pathways showed modest or no apparent changes in target gene expression. Expression levels of <i>Nkx2.1</i> and <i>Myc</i> were also significantly increased, similar to findings in human adenocarcinoma. Interestingly, expression of <i>Itgb4</i> (<i>integrin beta 4</i>) was also increased in tumor tissues. Future studies will determine whether Itgb4 plays a role in tumor development. (B) qPCR analysis of RNA extracted from representative human lung cancer cell lines, including NCI-H292 (pulmonary mucoepidermoid carcinoma), NCI-H82 (small cell lung cancer), NCI-H441 (papillary adenocarcinoma of the lung) and NCI-A549 (lung adenocarcinoma). The numbers represent fold of increase in marker expression relative to housekeeping genes. <i>SPC</i> expression was upregulated in the A549 cell line. <i>ITGB4</i> (<i>integrin beta 4</i>) was also highly expressed in non-small cell lung cancer cell lines compared to small-cell lung cancer cell lines.