Effect of DGAT knockdown on gene expression in A498 xenograft tumors

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. 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.