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Sphingosine-1-Phosphate Receptor Subtype 3: A Novel Therapeutic Target of K-Ras Mutant Driven Non-Small Cell Lung Carcinoma

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Technical Report,15 Sep 2014,14 Sep 2015

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Wayne State University Detroit United States

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This award aims to characterize the functional role of sphingosine-1-phosphate receptor subtype 3 S1PR3 in oncogenic K-Ras mutant-mediated lung adenocarcinoma AdC progression, and to examine the novel therapeutic utility for K-Ras mutant-driven lung AdC by targeting S1PR3. There are two specific aims. Aim 1 We will use the LSL-K-RasG12D mouse model to investigate the role of S1PR3 in the developmentmaintenance of lung AdC.LSL-K-RasG12D will be bred with mice null for S1PR3. S1PR3--LSL-K-RasG12D mice will be nasally instilled with adenoviral particle carrying Cre recombinase Ad-Cre to induce lung AdC. 3 months later, lung will be weighted, and lung tumor nodules will be quantitated. S1PR3 LSL-K-RasG12D mice will be used as a control. Aim 2 LSL-K-RasG12D mice will be instilled with Ad-Cre. Subsequently, TY-52156, a specific S1PR3 antagonist, will be i.p. injected every three days. Mice will be euthanized at 2 and 4 months. Hyperplasia of lung epithelial cells, development of lung adenomas and adenocarcinomas will be assessed. We have completed the animal treatments proposed in Aims 1 and 2. The collected mouse lung specimens are currently being analyzed.

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