Novel Functional Germline Variants in the VEGF Receptor 2 Gene and Their Effect on Gene Expression and Microvessel Density in Lung Cancer

摘要: Purpose: VEGFR-2 plays a crucial role in mediating angiogenic endothelial cell responses via the VEGF pathway and angiogenesis inhibitors targeting are clinical use. As is host-driven process, functional heritable variation KDR , gene encoding VEGFR-2, may affect function, ultimately, extent of tumor angiogenesis. Experimental Design: We resequenced using 24 DNAs each from healthy Caucasian, African American Asian groups. Non-synonymous genetic variants were assessed for function phosphorylation assays. Luciferase reporter assays used to examine effects on expression. mRNA protein expression, microvessel density (MVD) measured non-small lung cancer (NSCLC) samples matching patient DNA genotyped test associations with interest. Results: resequencing led discovery 120 variants, which 25 had not been previously reported. Q472H increased associated MVD NSCLC samples. -2854C -2455A luciferase expression higher levels -271A reduced lower -906C 23408G, Conclusions: This study has defined three populations identified common that impact tumoral vascularization. These findings have important implications understanding molecular basis between phenotypes related function.