Identification of gene expression signature modulated by nicotinamide in a mouse bladder cancer model.
BACKGROUND
Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice.


RESULTS
Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers.


CONCLUSIONS
This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer.
Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
Seon-Kyu
SK
Kim
Seok-Joong
SJ
Yun
Jiyeon
J
Kim
Ok-Jun
OJ
Lee
Suk-Chul
SC
Bae
Wun-Jae
WJ
Kim
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology*; D015203:Reproducibility of Results; D013045:Species Specificity; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control
D009536:Niacinamide; D002085:Butylhydroxybutylnitrosamine