Lactate Dehydrogenase B Is Required for the Growth of KRAS-Dependent Lung Adenocarcinomas
作者： Mark L. McCleland , Adam S. Adler , Laura Deming , Ely Cosino , Leslie Lee
DOI: 10.1158/1078-0432.CCR-12-2638
关键词:
摘要: Purpose: This study is aimed to identify genes within the KRAS genomic amplicon that are both coupregulated and essential for cell proliferation when amplified in lung cancer. Experimental Design: We used an integrated approach coamplified with adenocarcinomas subsequently preformed RNA interference (RNAi) screen uncover functionally relevant genes. The role of lactate dehydrogenase B (LDHB) was investigated vitro vivo by siRNA short hairpin (shRNA)–mediated knockdown a panel adenocarcinoma cells lines. LDHB expression also patient tumors using microarray immunohistochemistry analyses. Results: RNAi-mediated depletion abrogated xenografted . find correlates copy number gain mutation cancer lines adenocarcinomas. correlation between status specific cancers not other tumor types harbor mutations. Consistent glycolysis metabolism, KRAS-mutant exhibit elevated gene signature more dependent on compared wild-type tumors. Finally, high significant predictor shorter survival patients Conclusion: identifies as regulator subset may provide novel therapeutic treating Clin Cancer Res; 19(4); 773–84. ©2012 AACR
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