Purpose: Nicotinamide-N-methyltransferase(NNMT) is an enzyme involved in the metabolism of drugs and xenobiotic compounds. It is known to be highly expressed in a variety of cancers and has been investigated for its potential use as a diagnostic or prognostic marker. Furthermore, clinical data has shown that high NNMT expression is correlated with adverse patient outcome. In our glioblastoma (GBM) patient data set and other publically available data set NNMT is one among the top 25 genes which is differentially regulated when compared with normal adjacent tissue and also with various grades of brain tumor. NNMT is highly expressed in grade IV compared to low grade astrocytomas. Kaplan-Meier survival plots for NNMT gene shows that higher expression is associated with poor survival benefit and the median survival was found to be more than doubled in patient group with low expression of NNMT. Despite all this, the mechanistic behavior of NNMT in the malignant phenotype remains uncharacterized. We plan to gain an understanding of the signaling pathways with which NNMT interacts and elucidate its role in radioresistance.

Experimental Design: The in vitro radiosensitivity assays were evaluated using wild type, NNMT-knockdown and NNMT-overexpression GBM cell lines. The assay conducted includes MTS, DNA damage and repair, Clonogenic survival assay, comet assay, Annexin V apoptosis assay, matrigel invasion assays, ATP assay, etc. The cell line after treatment was lysed and probed for pro-and anti-survival signaling pathways.

Results and Discussion: We explored the expression profile of NNMT in established (ATCC) and in our panel of primary GBM cell lines. The expression levels correlates with relative radioresistance exhibited by the cell line. It appears NNMT knockdown cell lines exhibited an enhanced radiosensitivity. Currently we are probing signaling cascades which are differentially regulated in the NNMT knockdown and overexpression cell lines and also the differential response to radiation treatment based on differing levels of NNMT expression. The results will be presented at the meeting.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-165.