Abstract
Abstract NDN is a maternally imprinted gene on chromosome 15q11.2 that is consistently expressed in normal ovarian epithelium, but dramatically downregulated in the majority of ovarian cancer cell lines and surgical specimens, determined by gene expression array and RT-PCR analysis. On tissue microarrays, little or no NDN protein could be detected by immunohistochemical analysis in73% of 351 epithelial ovarian cancers. Loss of NDN expression could be attributed, in part, to LOH in 28% of 18 informative cases and to hypermethylation of CpG sites 1 and 2 in the NDN promoter region in 21% and 27% of 43 ovarian cancers, respectively. All hypermethylated cases were associated with NDN down-regulation. Promoter hypermethylation and decreased NDN expression were also found in 7 of 10 ovarian cancer cell lines. Treatment with the demethylating agent decitabine increased NDN expression in 4 of 7 hypermethylated cell lines. Treatment with the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased NDN expression in 2 cell lines with normal or reduced methylation. However, when the two drugs were combined, they didn't show additive or synergistic effect. Re-expression of NDN in ovarian cancer cell lines such as SKOv3 and HEY significantly inhibited cell growth, associated with apoptosis, but not autophagy or necrosis. Re-expression of NDN also inhibited cell migration. These observations support the hypothesis that NDN is an imprinted tumor suppressor gene and its loss of function can be caused by multiple mechanisms in ovarian cancer. Citation Format: Hailing Yang, Partha Das, Yinhua Yu, Keith Baggerly, Ying Wang, Weiqun Mao, Rebecca T. Marquez, Zhen Lu, Jinsong Liu, Robert C. Bast. NDN, an imprinted tumor suppressor gene inhibits ovarian cancer cell growth and motility and is downregulated by genetic and epigenetic mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2311. doi:10.1158/1538-7445.AM2014-2311
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