Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines.

Abstract

We recently used RNA interference to show that a negative correlation of L-asparaginase (L-ASP) chemotherapeutic activity with asparagine synthetase (ASNS) expression in the ovarian subset of the NCI-60 cell line panel is causal. To determine whether that relationship would be sustained in a larger, more diverse set of ovarian cell lines, we have now measured ASNS mRNA expression using microarrays and a branched-DNA RNA assay, ASNS protein expression using an electrochemiluminescent immunoassay, and L-ASP activity using an MTS assay on 19 human ovarian cancer cell lines. Contrary to our previous findings, L-ASP activity was only weakly correlated with ASNS mRNA expression; Pearson's correlation coefficients were r = -0.21 for microarray data and r = -0.39 for the branched-DNA RNA assay, with just the latter being marginally statistically significant (P = 0.047, one-tailed). ASNS protein expression measured by liquid-phase immunoassay exhibited a much stronger correlation (r = -0.65; P = 0.0014, one-tailed). We conclude that ASNS protein expression measured by immunoassay is a strong univariate predictor of L-ASP activity in ovarian cancer cell lines. These findings provide rationale for evaluation of ASNS protein expression as a predictive biomarker of clinical L-ASP activity in ovarian cancer.

• Authors: Philip L Lorenzi, Jenny Llamas, Michele Gunsior, Laurent Ozbun, William C Reinhold, Sudhir Varma, Helen Ji, Hijoo Kim, Amy A Hutchinson, Elise C Kohn, Paul K Goldsmith, Michael J Birrer, John N Weinstein
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 7 Issue 10 Pg. 3123-8 (Oct 2008) ISSN: 1535-7163 [Print] United States
• PMID: 18852115 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• Asparaginase
• Aspartate-Ammonia Ligase

Topics

• Asparaginase (metabolism)
• Aspartate-Ammonia Ligase (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Cell Line, Tumor
• DNA Fingerprinting
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Oligonucleotide Array Sequence Analysis
• Ovarian Neoplasms (enzymology, genetics)
• RNA, Messenger (genetics, metabolism)