ZNF703 acts as an oncogene that promotes progression in gastric cancer

Yang,Gongli; Ma,Feng; Zhong,Muxiao; Fang,Lin; Peng,Yao; Xin,Xiaoming; Zhong,Jietao; Yuan,Fangfang; Gu,Hongxiang; Zhu,Wei; Zhang,Yali

doi:10.3892/or.2014.2997

ZNF703 acts as an oncogene that promotes progression in gastric cancer

Authors:
- Gongli Yang
- Feng Ma
- Muxiao Zhong
- Lin Fang
- Yao Peng
- Xiaoming Xin
- Jietao Zhong
- Fangfang Yuan
- Hongxiang Gu
- Wei Zhu
- Yali Zhang
View Affiliations

Affiliations: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: January 24, 2014 https://doi.org/10.3892/or.2014.2997
Pages: 1877-1882

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

ZNF703, a member of the NET/Nlz family of zinc finger transcription factors, contributes to aspects of developmental growth and patterning across evolutionarily diverse species. ZNF703 has been identified as a novel oncogene in human breast cancer. In the present study, we investigated the expression of ZNF703 in gastric carcinoma and attempted to determine, using cell line models, its biological actions. Using immunohistochemistry, we analyzed the ZNF703 protein expression in 120 clinicopathologically characterized gastric cancer cases. Using RNA interference, we investigated the effects of ZNF703 depletion on tumor proliferation and metastasis in vitro. We found that ZNF703 was overexpressed in invasive gastric carcinoma tissues, and its expression levels were closely correlated with the depth of invasion, node metastasis and venous invasion. RNA interference-mediated silencing of the ZNF703 gene in SGC7901 cells inhibited cell proliferation and migration significantly. The results showed that ZNF703 acts as a gastric cancer oncogene and should be considered a therapeutic target for metastatic gastric cancer.

View Figures

View References

1	Hartgrink HH, Jansen EP, van Grieken NC and van de Velde CJ: Gastric cancer. Lancet. 374:477–490. 2009. View Article : Google Scholar
2	Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A and Fleig WE: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 24:2903–2909. 2006. View Article : Google Scholar : PubMed/NCBI
3	Goseki N, Koike M and Yoshida M: Histopathologic characteristics of early stage esophageal carcinoma. A comparative study with gastric carcinoma. Cancer. 69:1088–1093. 1992. View Article : Google Scholar : PubMed/NCBI
4	Nakamura M, Runko AP and Sagerström CG: A novel subfamily of zinc finger genes involved in embryonic development. J Cell Biochem. 93:887–895. 2004. View Article : Google Scholar : PubMed/NCBI
5	Dorfman R, Glazer L, Weihe U, Wernet MF and Shilo BZ: Elbow and Noc define a family of zinc finger proteins controlling morphogenesis of specific tracheal branches. Development. 129:3585–3596. 2002.PubMed/NCBI
6	Zhao X, Yang Y, Fitch DH and Herman MA: TLP-1 is an asymmetric cell fate determinant that responds to Wnt signals and controls male tail tip morphogenesis in C. elegans. Development. 129:1497–1508. 2002.PubMed/NCBI
7	Runko AP and Sagerström CG: Nlz belongs to a family of zinc-finger-containing repressors and controls segmental gene expression in the zebrafish hindbrain. Dev Biol. 262:254–267. 2003. View Article : Google Scholar : PubMed/NCBI
8	Gerhard DS, Wagner L, Feingold EA, et al: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 14:2121–2127. 2004. View Article : Google Scholar : PubMed/NCBI
9	Chin K, DeVries S, Fridlyand J, et al: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 10:529–541. 2006. View Article : Google Scholar : PubMed/NCBI
10	Holland DG, Burleigh A, Git A, et al: ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med. 3:167–180. 2011. View Article : Google Scholar
11	Sircoulomb F, Nicolas N, Ferrari A, et al: ZNF703 gene amplification at 8p12 specifies luminal B breast cancer. EMBO Mol Med. 3:153–166. 2011. View Article : Google Scholar
12	Eriksson N, Benton GM, Do CB, et al: Genetic variants associated with breast size also influence breast cancer risk. BMC Med Genet. 13:532012. View Article : Google Scholar : PubMed/NCBI
13	Slorach EM, Chou J and Werb Z: Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization. Genes Dev. 25:471–484. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lauren P: The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 64:31–49. 1965.PubMed/NCBI
15	Goseki N, Takizawa T and Koike M: Differences in the mode of the extension of gastric cancer classified by histological type: new histological classification of gastric carcinoma. Gut. 33:606–612. 1992. View Article : Google Scholar : PubMed/NCBI
16	Fenoglio-Preiser CM, Noffsinger AE, Stemmermann GN, et al: Gastrointestinal Pathology: An Atlas and Text. Raven Press; New York: 1989
17	Hamilton SR and Aaltonen LA: Pathology and Genetics Tumours of the Digestive System. World Health Organization Classification of Tumours. IARC Press; Lyon: 2000
18	Trainer DL, Kline T, McCabe FL, et al: Biological characterization and oncogene expression in human colorectal carcinoma cell lines. Int J Cancer. 41:287–296. 1988. View Article : Google Scholar : PubMed/NCBI
19	Reynisdottir I, Arason A, Einarsdottir BO, et al: High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer. Cancer Med. 2:437–446. 2013.
20	Spellman P and Gray J: A new treasure in the breast cancer gene hunt. Nat Med. 17:422–423. 2011. View Article : Google Scholar : PubMed/NCBI
21	Nakamura M, Choe SK, Runko AP, Gardner PD and Sagerström CG: Nlz1/Znf703 acts as a repressor of transcription. BMC Dev Biol. 8:1082008. View Article : Google Scholar : PubMed/NCBI
22	Pereira-Castro I, Costa AM, Oliveira MJ, et al: Characterization of human NLZ1/ZNF703 identifies conserved domains essential for proper subcellular localization and transcriptional repression. J Cell Biochem. 114:120–133. 2013. View Article : Google Scholar
23	Bazarov AV and Yaswen P: Who is in the driver’s seat in 8p12 amplifications? ZNF703 in luminal B breast tumors. Breast Cancer Res. 13:3082011.
24	Zhang X, Mu X, Huang O, et al: Luminal breast cancer cell lines overexpressing ZNF703 are resistant to tamoxifen through activation of Akt/mTOR signaling. PLoS One. 8:e720532013. View Article : Google Scholar : PubMed/NCBI
25	Gelsi-Boyer V, Orsetti B, Cervera N, et al: Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 3:655–667. 2005. View Article : Google Scholar : PubMed/NCBI