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Int J Clin Exp Pathol 2010;3(5):522-527

Original Article
Overexpression of niotinamide phosphoribosyltransferase in ovarian cancers

Rodney E. Shackelford, Marilyn M. Bui, Domenico Coppola, Ardeshir Hakam

Department of Pathology and Cell Biology, University of South Florida, 12901 Bruce B. Downs Blvd, MDC Box 11, Tampa, FL 33612-4799,
United States. Department of Anatomic Pathology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, Florida,
33612, United States.

Received April 27, 2010, accepted April, 2010, available April, 2010

Abstract: 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 ovarian serous
adenocarcinomas 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. (IJCEP1004011).

Key words: Nicotinamide phosphoribosyltransferase, serous adenocarcinoma, ovarian cancer, nicotinamide adenine dinucleotide, Stat3,
interleukin-6

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Address all correspondence to:
Ardeshir Hakam, MD
Department of Anatomic Pathology
H. Lee Moffitt Cancer Center & Research Institute
12902 Magnolia Drive
Tampa, Florida, 33612
USA.
E-mail:
Ardeshir.Hakam@moffitt.org