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Medical Oncology
Erschienen in: Medical Oncology 4/2013

01.12.2013 | Original Paper

Expression and role of grainyhead-like 2 in gastric cancer

Erschienen in: Medical Oncology | Ausgabe 4/2013

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Abstract

The aim of this study was to evaluate the expression and role of Grhl2 in gastric cancer. Immunohistochemistry was performed to explore the expression of Grhl2 in gastric cancer and surrounding non-tumor tissues. Moreover, the mRNA and protein expression level of Grhl2 in human immortalized gastric epithelial cell line GES-1 and four gastric cancer cell lines (MGC803, SGC7901, MKN45, HGC27) were detected by qRT-PCR and Western blotting, respectively. To further investigate the role of Grhl2 in gastric cancer as well as the potential mechanisms, SGC7901 cells were transfected with lentiviral constructs expressing Grhl2 or empty vector, and then proliferation and apoptosis of SGC7901 cells were evaluated by MTT assay and flow cytometry, respectively. Finally, the protein expression level of c-Myc and Bcl-2 was detected by Western blotting. Both mRNA and protein expression level of Grhl2 were significantly downregulated in gastric cancer. Exogenous Grhl2 transduced into SGC7901 cells significantly inhibited the proliferation and promoted apoptosis. Meanwhile, over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. Taken together, our results demonstrated that Grhl2 downregulated in gastric cancer and may function as a tumor suppressor and play an important role in the development and progression of gastric cancer. These results may provide a new clue for treatment for gastric cancer.
Literatur
1.
Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M. Comparative risk assessment collaborating group (cancers) causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet. 2005;366:1784–93.CrossRefPubMed
2.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRefPubMed
3.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRefPubMed
4.
5.
Wilanowski T, Tuckfield A, Cerruti L, O’Connell S, Saint R, Parekh V, Tao J, et al. A highly conserved novel family of mammalian developmental transcription factors related to drosophila grainyhead. Mech Dev. 2002;114:37–50.CrossRefPubMed
6.
Werth M, Walentin K, Aue A, Schönheit J, Wuebken A, Pode-Shakked N, Vilianovitch L, et al. The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex. Development. 2010;137:3835–45.CrossRefPubMed
7.
Pyrgaki C, Liu A, Niswander L. Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion. Dev Biol. 2011;353:38–49.CrossRefPubMedCentralPubMed
8.
Senga K, Mostov KE, Mitaka T, Miyajima A, Tanimizu N. Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25. Mol Biol Cell. 2012;23:2845–55.CrossRefPubMedCentralPubMed
9.
Gao X, Vockley CM, Pauli F, Newberry KM, Xue Y, Randell SH, Reddy TE, et al. Evidence for multiple roles for grainyheadlike 2 in the establishment and maintenance of human mucociliary airway epithelium. Proc Natl Acad Sci USA. 2013;110:9356–61.CrossRefPubMedCentralPubMed
10.
Tanaka Y, Kanai F, Tada M, Tateishi R, Sanada M, Nannya Y, Ohta M, et al. Gain of GRHL2 is associated with early recurrence of hepatocellular carcinoma. J Hepatol. 2008;49:746–57.CrossRefPubMed
11.
Kang X, Chen W, Kim RH, Kang MK, Park NH. Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells. Oncogene. 2009;28:565–74.CrossRefPubMedCentralPubMed
12.
Cieply B, Riley P 4th, Pifer PM, Widmeyer J, Addison JB, Ivanov AV, Denvir J, et al. Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2. Cancer Res. 2012;72:2440–53.CrossRefPubMedCentralPubMed
13.
Yang X, Vasudevan P, Parekh V, Penev A, Cunningham JM. Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis. PLoS One. 2013;8:e56195.CrossRefPubMedCentralPubMed
14.
Xiang X, Deng Z, Zhuang X, Ju S, Mu J, Jiang H, Zhang L, et al. Correction: Grhl2 determines the epithelial phenotype of breast cancers and promotes tumor progression. PLoS One. 2013; 8.
15.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed
16.
Zha L, Zhang J, Tang W, Zhang N, He M, Guo Y, Wang Z. HMGA2 elicits EMT by activating the Wnt/β-catenin pathway in gastric cancer. Dig Dis Sci. 2013;58:724–33.CrossRefPubMed
17.
Han S, Kim HY, Park K, Cho HJ, Lee MS, Kim HJ, Kim YD. c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer. J Korean Med Sci. 1999;14:526–30.CrossRefPubMedCentralPubMed
18.
Guo J, Xiao B, Liu Q, Gong Z, Le Y. Suppression of c-Myc expression associates with anti-proliferation of aloe-emodin on gastric cancer cells. Cancer Invest. 2008;26:369–74.CrossRefPubMed
19.
20.
Ting SB, Wilanowski T, Cerruti L, Zhao LL, Cunningham JM, Jane SM. The identification and characterization of human sister-of-mammalian grainyhead (SOM) expands the grainyhead-like family of developmental transcription factors. Biochem J. 2003;370:953–62.CrossRefPubMedCentralPubMed
21.
Auden A, Caddy J, Wilanowski T, Ting SB, Cunningham JM, Jane SM. Spatial and temporal expression of the grainyhead-like transcription factor family during murine development. Gene Expr Patterns. 2006;6:964–70.CrossRefPubMed
22.
Boglev Y, Wilanowski T, Caddy J, Parekh V, Auden A, Darido C, Hislop NR, et al. The unique and cooperative roles of the grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity. Dev Biol. 2011;349:512–22.CrossRefPubMed
23.
Brouns MR, De Castro SC, Terwindt-Rouwenhorst EA, Massa V, Hekking JW, Hirst CS, Savery D, et al. Over-expression of Grhl2 causes spina bifida in the axial defects mutant mouse. Hum Mol Genet. 2011;20:1536–46.CrossRefPubMedCentralPubMed
24.
Van Laer L, Van Eyken E, Fransen E, Huyghe JR, Topsakal V, Hendrickx JJ, Hannula S, et al. The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. Hum Mol Genet. 2008;17:159–69.CrossRefPubMed
25.
Peters LM, Anderson DW, Griffith AJ, Grundfast KM, San Agustin TB, Madeo AC, Friedman TB, et al. Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28. Hum Mol Genet. 2002;11:2877–85.CrossRefPubMed
26.
Han Y, Mu Y, Li X, Xu P, Tong J, Liu Z, Ma T, et al. Grhl2 deficiency impairs otic development and hearing ability in a zebrafish model of the progressive dominant hearing loss DFNA28. Hum Mol Genet. 2011;20:3213–26.CrossRefPubMed
27.
Chen W, Dong Q, Shin KH, Kim RH, Oh JE, Park NH, Kang MK. Grainyhead-like 2 enhances the human telomerase reverse transcriptase gene expression by inhibiting DNA methylation at the 5′-CpG island in normal human keratinocytes. J Biol Chem. 2010;285:40852–63.CrossRefPubMedCentralPubMed
28.
Dompe N, Rivers CS, Li L, Cordes S, Schwickart M, Punnoose EA, Amler L, et al. A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis. Proc Natl Acad Sci USA. 2011;108:E943–51.CrossRefPubMedCentralPubMed
29.
Chen W, Xiao Liu Z, Oh JE, Shin KH, Kim RH, Jiang M, Park NH, et al. Grainyhead-like 2 (GRHL2) inhibits keratinocyte differentiation through epigenetic mechanism. Cell Death Dis. 2012;3:e450.
30.
31.
Darido C, Georgy SR, Wilanowski T, Dworkin S, Auden A, Zhao Q, Rank G, et al. Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell. 2011;20:635–48.CrossRefPubMed
32.
Bhandari A, Gordon W, Dizon D, Hopkin AS, Gordon E, Yu Z, Andersen B. The Grainyhead transcription factor Grhl3/Get1 suppresses miR-21 expression and tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding protein DND1. Oncogene. 2013;32:1497–507.CrossRefPubMedCentralPubMed
33.
Guardiola-Serrano F, Haendeler J, Lukosz M, Sturm K, Melchner HV, Altschmied J. Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration. Biochem Biophys Res Commun. 2008;376:748–52.CrossRefPubMed
Metadaten
Titel
Expression and role of grainyhead-like 2 in gastric cancer
Publikationsdatum
01.12.2013
Erschienen in
Medical Oncology / Ausgabe 4/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0714-5

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