Research Description

ASNS Gene Regulation in Jensen Rat Sarcoma Cells

Asparaginase (ASNase) is a drug involved in the treatment of childhood acute lymphoblastic leukemia (ALL). ASNase acts by reducing serum levels of the amino acid asparagine. In most cells, asparagine is synthesized by the enzyme asparagine synthetase (ASNS), and is thus nutritionally nonessential. The expression of ASNS protein, as studied by the Kilberg Laboratory, has been found to correlate with ASNase resistance. The majority of ALL cell lines, however, demonstrate low expression of ASNS. As such, ASNase can specifically target the cancer cells and act as effective treatment.

Jensen rat sarcoma cells (JRS) are cancer cells that have lost the ability to produce asparagine due to methylation of the ASNS gene. However, when treated with 5-azacytidine, a chemical known to demethylate genes by inhibiting DNA methyl transferases, JRS cells produce ASNS protein and regain the ability to produce their own asparagine. The focus of my project will be to characterize this cell line, with the goal of learning more about the regulation of the ASNS gene in these cells. By contrasting the wild type JRS cells with the 5-azacytidine revertants, I will look at transcription factors present at the gene under varying conditions, so as to further understand the regulation mechanisms involved in ASNS expression and repression. I additionally hope to compare my studies of ASNS in JRS cells to human sarcoma cell lines, so as to extend the possibility of ASNase treatment for additional cancers and diseases.