Over-expression of nicotinamide phosphoribosyltransferase in ovarian cancers.
Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide (NAD(+)) synthesis and is required for cell growth, survival, DNA replication and repair, and angiogenesis. Nampt expression increases gene expression which promotes cell survival and increases SirT1 activity, promoting angiogenesis, and it is increased in several human malignancies. Recently, others have shown that ovarian serous adenocarcinomas (OSAs) express high levels of activated Stat3. Since Nampt expression is increased by Stat3, we hypothesized that Nampt protein might be highly expressed in OSAs. Using tissue microarray (TMA) and the avidin-biotin complex immunohistochemical technique we examined Nampt expression in 47 samples of benign ovarian tissue and 49 samples of ovarian serous adenoacarcinomas. Our data show that Nampt protein expression is significantly increased in OSAs as compared to benign ovarian tissue (0.49+/-0.12 benign vs. 4.78+/-0.46 malignant; +/-standard error of the mean). This is the first report demonstrating Nampt overexpression in OSA, which may shed light on the pathogenesis of OSA. Further studies of the role of Nampt overexpresion in OSA may shed light on the prognosis and clinical course of OSA. Last, since an effective pharmacologic Nampt inhibitor is currently in clinical use, further studies of Nampt overexpression in OSA may be used in selecting patients for Nampt inhibitor therapy.
Shackelford
Rodney E
RE
Department of Pathology and Cell Biology, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL, USA.
Bui
Marilyn M
MM
Coppola
Domenico
D
Hakam
Ardeshir
A
D014408:Biomarkers, Tumor / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D054409:Nicotinamide Phosphoribosyltransferase / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000201:enzymology*; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human