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This study compares high resolution forward models of natural gamma-ray background with that measured by high resolution aerial gamma-ray surveys. The ability to predict variations in natural background radiation levels should prove useful for those engaged in measuring anthropogenic contributions to background radiation for the purpose of emergency response and homeland security operations. The forward models are based on geologic maps and remote sensing multi-spectral imagery combined with two different sources of data: 1) bedrock geochemical data (uranium, potassium and thorium concentrations) collected from national databases, the scientific literature and private companies, and 2) the low spatial resolution NURE (National Uranium Resource Evaluation) aerial gamma-ray survey. The study area near Cameron, Arizona, is located in an arid region with minimal vegetation and, due to the presence of abandoned uranium mines, was the subject of a previous high resolution gamma-ray survey. We found that, in general, geologic map units form a good basis for predicting the geographic distribution of the gamma-ray background. Predictions of background gamma-radiation levels based on bedrock geochemical analyses were not as successful as those based on the NURE aerial survey data sorted by geologic unit. The less successful result of the bedrock geochemical model is most likely due to a number of factors including the need to take into account the evolution of soil geochemistry during chemical weathering and the influence of aeolian addition. Refinements to the forward models were made using ASTER visualizations to create subunits of similar exposure rate within the Chinle Formation, which contains multiple lithologies and by grouping alluvial units by drainage basin rather than age.

The Hippo signaling pathway was initially identified in Drosophila and components in this pathway are highly conserved in mammals. We and others have recently shown that the Hippo pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers, where it promotes epithelial to mesenchymal transition (EMT) and malignant transformation. To date, studies of YAP target genes have focused on cellautonomous mediators. Here, we show that YAP-expressing MCF10A breast epithelial cells secrete growth factors that enhance the proliferation of neighboring untransfected cells, implicating a non-cell autonomous mechanism. Using cytokine and growth factor array analysis, we identified the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG), as a transcriptional target of YAP, whose induction contributes to YAP-mediated cell proliferation and migration. Knockdown of AREG or addition of an EGFR kinase inhibitor abrogates the proliferative effects of YAP expression. Suppression of the negative YAP regulators LATS1/2 is sufficient to induce AREG expression, consistent with a physiological regulation of AREG by the Hippo pathway. Furthermore, genetic interactions between the Drosophila YAP orthologue Yki and Egfr signaling components support the link between these two highly conserved signaling pathways. In conclusion, YAP-dependent secretion of AREG implicates activation of EGFR signaling as an important non-cell autonomous effector of the Hippo pathway, with relevance for the regulation of both physiological and malignant cell proliferation. Citation Information: Cancer Res 2009;69(23 Suppl):A12.

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