BCAT1 expression associates with ovarian cancer progression

Previously, we have identified cytosolic form of the branched chain amino-acid transaminase 1 (BCAT1) as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous EOC tumors, thus suggesting that epigenetic mechanisms might be implicated in BCAT1 overexpression in serous epithelial ovarian cancer (EOC). Knockdown of the BCAT1 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, BCAT1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon BCAT1 suppression, while some tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the BCAT1 gene in advanced EOC and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target. To better understand the molecular mechanisms of BCAT1 gene action in ovarian cancer cells, we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon BCAT1 suppression in SKOV3 cells. We compared the gene expression of the previously selected clone shRNA-mediated BCAT1-knockdown SKOV3 clones B1 & B2 (sh-clB1 & sh-clB2) against the corresponding control (ctrl) clone. The microarray experiments were performed in duplicates, as four hybridizations were carried out for the BCAT1-suppressing cell clones against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.