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Effect of DGAT knockdown on gene expression in A498 xenograft tumors

ABSTRACT: The metabolic enzyme diglyceride acyltransferase (DGAT) is responsible for the synthesis of triglycerides. Loss of its expression may sensitize cells to conditions of nutrient and oxygen that are commonly present in tumors. This study is designed to identify stress response pathways that may be induced following the shRNA-mediated knockdown of the two genes coding for the DGAT enzymes. We used microarrays to detail the global programme of gene expression following DGAT knockdown in vivo and identified differentially regulated gene sets. Overall design: A cell line was created from A498 ccRCC cells that effectively knocks down DGAT levels upon doxycycline administration. This cell line was used to grow subcutaneous tumors in NIH-III mice, which were then treated with doxycycline containing chow (200mg/kg) or control chow for 5 days before tumors were harvested and RNA was isolated for this microarray study.

INSTRUMENT(S): [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]

SUBMITTER: Daniel Ackerman  

PROVIDER: GSE117774 | GEO | 2018-07-28


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Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.

Ackerman Daniel D   Tumanov Sergey S   Qiu Bo B   Michalopoulou Evdokia E   Spata Michelle M   Azzam Andrew A   Xie Hong H   Simon M Celeste MC   Kamphorst Jurre J JJ  

Cell reports 20180901 10

Lipid droplets, which store triglycerides and cholesterol esters, are a prominent feature of clear cell renal cell carcinoma (ccRCC). Although their presence in ccRCC is critical for sustained tumorigenesis, their contribution to lipid homeostasis and tumor cell viability is incompletely understood. Here we show that disrupting triglyceride synthesis compromises the growth of both ccRCC tumors and ccRCC cells exposed to tumor-like conditions. Functionally, hypoxia leads to increased fatty acid s  ...[more]

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