Home LiteratureArticle Details
PMID: 26823742 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Methylation-silencing RCC1 expression is associated with tumorigenesis and depth of invasion in gastric cancer.

International journal of clinical and experimental pathology ·Vol. 8 ·No. 11 ·2015-00-00 ·Pages 14257-69

Lin YL, Chen HL, Cheng SB, Yeh DC, Huang CC, P'eng FK, Tsai TC, Wu CC, Chen CM

Abstract

Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator. We firstly identified RCC1 gene hypermethylation in gastric tumor tissues using the differential methylation hybridization (DMH) microarray, but the role of RCC1 in the pathogenesis of gastric carcinoma is largely unknown. Three gastric cancer cell lines (AGS, MKN45, and TSGH9201) were used to analyze RCC1 gene methylation, mRNA and protein expressions. Furthermore, 85 pairs of matched human gastric carcinoma samples in a tissue microarray were used to analyze RCC1 expression by immunohistochemistry staining. A differential methylation pattern was found in TSGH9201 (100%), MKN45 (87%), and AGS (62%) cell lines at the 9th CpG site of RCC1 exon 1. RCC1 mRNA and protein expressions in AGS cells were significantly higher than in TSGH9201 and MKN45 cell lines (P < 0.05). Tissue array data showed that RCC1 expression was detected in 21% (18/85) of gastric carcinoma tissues and in 80% (76/95) of adjacent non-tumor tissues. The expression of RCC1 in gastric carcinoma tissues was significantly lower than in adjacent non-tumor tissues (P < 0.001). Furthermore, an association between RCC1 expression and clinicopathological features showed that RCC1 expression was closely correlated with tumor differentiation and depth of invasion (P < 0.05). Our data indicate that RCC1 expression is frequently lost in poorly differentiated gastric cell lines and gastric carcinoma tissues. Loss of RCC1 expression is correlated with tumor differentiation and depth of invasion. These findings suggest that RCC1 may play a tumor suppressor role in gastric carcinoma.

Keywords
DMH microarray DNA methylation RCC1 gastric carcinoma immunohistochemistry invasion tumor tissue array
MeSH Terms
Base Sequence Carcinogenesis/genetics,metabolism,pathology Carcinoma/genetics,metabolism,secondary Cell Cycle Proteins/genetics,metabolism Cell Differentiation Cell Line, Tumor Cell Movement CpG Islands DNA Methylation Down-Regulation Female Gene Expression Regulation, Neoplastic Gene Silencing Guanine Nucleotide Exchange Factors/genetics,metabolism Humans Immunohistochemistry Male Middle Aged Molecular Sequence Data Neoplasm Grading Neoplasm Invasiveness Nuclear Proteins/genetics,metabolism RNA, Messenger/genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stomach Neoplasms/genetics,metabolism,pathology Tissue Array Analysis Transfection Tumor Suppressor Proteins/genetics,metabolism
Chemicals
Cell Cycle Proteins Guanine Nucleotide Exchange Factors Nuclear Proteins RCC1 protein, human RNA, Messenger Tumor Suppressor Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lin Yi-Ling
Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing UniversityTaichung 402, Taiwan; Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan.
Chen Hsiao-Ling
Department of Bioresources, Da-Yeh University Changhwa 515, Taiwan.
Cheng Shao-Bin
Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan; School of Medicine, Chung-Shan Medical UniversityTaichung 402, Taiwan.
Yeh Dah-Cherng
Department of General Surgery, Taichung Veterans General Hospital Taichung 407, Taiwan.
Huang Chu-Chun
Department of General Surgery, Taichung Veterans General Hospital Taichung 407, Taiwan.
P'eng Fang-Ku
Department of Surgery, Faculty of Medicine, National Yang-Ming University Taipei 112, Taiwan.
Tsai Tung-Chou
Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University Taichung 402, Taiwan.
Wu Cheng-Chung
Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan; Department of Surgery, Faculty of Medicine, National Yang-Ming UniversityTaipei 112, Taiwan; Department of Surgery, Chung-Shan Medical UniversityTaichung 402, Taiwan; Department of Surgery, Taipei Medical UniversityTaipei 110, Taiwan.
Chen Chuan-Mu
Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing UniversityTaichung 402, Taiwan; Rong-Hsing Translational Medicine Center, and iEGG Center, National Chung Hsing UniversityTaichung 402, Taiwan.
References (49)
49 references, click to expand
  1. High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.
    Am J Pathol. 2000 Sep;157(3):787-94 PMID: 10980118
  2. The Drosophila RCC1 homolog, Bj1, regulates nucleocytoplasmic transport and neural differentiation during Drosophila development.
    Dev Biol. 2004 Jun 1;270(1):106-21 PMID: 15136144
  3. Frequent epigenetic silencing of the folate-metabolising gene cystathionine-beta-synthase in gastrointestinal cancer.
    PLoS One. 2012;7(11):e49683 PMID: 23152928
  4. FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration.
    PLoS One. 2014;9(3):e90818 PMID: 24595062
  5. The human CHC1 gene encoding RCC1 (regulator of chromosome condensation) (CHC1) is localized to human chromosome 1p36.1.
    Genomics. 1994 Oct;23(3):719-21 PMID: 7851910
  6. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.
    PLoS One. 2015;10(2):e0115968 PMID: 25700270
  7. Loss of RCC1, a nuclear DNA-binding protein, uncouples the completion of DNA replication from the activation of cdc2 protein kinase and mitosis.
    EMBO J. 1991 Jun;10(6):1555-64 PMID: 1851087
  8. Lung tumorigenesis induced by human vascular endothelial growth factor (hVEGF)-A165 overexpression in transgenic mice and amelioration of tumor formation by miR-16.
    Oncotarget. 2015 Apr 30;6(12):10222-38 PMID: 25912305
  9. Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays.
    Cancer Res. 2001 Dec 1;61(23):8375-80 PMID: 11731411
  10. Gastric cancer.
    Lancet. 2009 Aug 8;374(9688):477-90 PMID: 19625077
  11. Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection.
    Vaccine. 2008 Jun 2;26(23):2882-9 PMID: 18450335
  12. Activator-mediated disruption of sequence-specific DNA contacts by the general transcription factor TFIIB.
    Genes Dev. 2001 Nov 15;15(22):2945-9 PMID: 11711430
  13. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer.
    Int J Cancer. 2011 Dec 1;129(11):2600-10 PMID: 21960261
  14. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  15. Cancer development and its natural history. A cancer prevention perspective.
    Cancer. 1988 Oct 15;62(8 Suppl):1676-9 PMID: 3167785
  16. 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. 1965;64:31-49 PMID: 14320675
  17. Methylation target array for rapid analysis of CpG island hypermethylation in multiple tissue genomes.
    Am J Pathol. 2003 Jul;163(1):37-45 PMID: 12819009
  18. Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection.
    World J Gastroenterol. 2015 Apr 28;21(16):4954-60 PMID: 25945009
  19. Immunohistochemical biomarkers in gastric cancer research and management.
    Int J Surg Oncol. 2012;2012:868645 PMID: 22778942
  20. Recent patterns in gastric cancer: a global overview.
    Int J Cancer. 2009 Aug 1;125(3):666-73 PMID: 19382179
  21. Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation.
    Genes Dev. 1987 Aug;1(6):585-93 PMID: 3678831
  22. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1.
    Nature. 1991 Nov 7;354(6348):80-2 PMID: 1944575
  23. Review article: intestinal metaplasia and gastric carcinogenesis.
    Aliment Pharmacol Ther. 2002 Jul;16(7):1209-16 PMID: 12144569
  24. Comparison of solid-state-cultured and wood-cultured Antrodia camphorata in anti-inflammatory effects using NF-κB/luciferase inducible transgenic mice.
    Phytomedicine. 2014 Oct 15;21(12):1708-16 PMID: 25442281
  25. Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening.
    J Pathol. 2004 Jun;203(2):681-7 PMID: 15141383
  26. Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances.
    Gan. 1968 Jun;59(3):251-8 PMID: 5726267
  27. Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach.
    Histopathology. 2005 May;46(5):505-14 PMID: 15842632
  28. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention.
    Cancer Res. 1992 Dec 15;52(24):6735-40 PMID: 1458460
  29. Phenotypic and genotypic events in gastric carcinogenesis.
    Cancer Res. 1994 Apr 1;54(7 Suppl):1941s-1943s PMID: 8137316
  30. Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma.
    Hum Mol Genet. 1992 Nov;1(8):559-63 PMID: 1338691
  31. NOR1 is an HSF1- and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma.
    Carcinogenesis. 2011 Sep;32(9):1305-14 PMID: 21803736
  32. The androgen receptor gene is preferentially hypermethylated in follicular non-Hodgkin's lymphomas.
    Clin Cancer Res. 2003 Sep 15;9(11):4034-42 PMID: 14519624
  33. Amplification of c-myc, K-sam, and c-met in gastric cancers: detection by fluorescence in situ hybridization.
    Lab Invest. 1998 Sep;78(9):1143-53 PMID: 9759658
  34. Establishment and characterization of TSGH9201, a human gastric carcinoma cell line that is growth inhibited by epidermal growth factor.
    J Surg Oncol. 1995 Jan;58(1):17-24 PMID: 7823569
  35. Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives.
    Cancer. 2000 Apr 15;88(8):1801-6 PMID: 10760755
  36. Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway.
    Oncotarget. 2014 Dec 15;5(23):12273-90 PMID: 25401518
  37. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
    Int J Cancer. 2010 Dec 15;127(12):2893-917 PMID: 21351269
  38. Expressed CpG island sequence tag microarray for dual screening of DNA hypermethylation and gene silencing in cancer cells.
    Cancer Res. 2002 Jun 1;62(11):3214-20 PMID: 12036936
  39. Applications of CpG island microarrays for high-throughput analysis of DNA methylation.
    J Nutr. 2002 Aug;132(8 Suppl):2430S-2434S PMID: 12163706
  40. von Hippel-Lindau exonic methylation analysis using MALDI-TOF mass spectrometry.
    J Urol. 2014 Nov;192(5):1528-33 PMID: 24704013
  41. Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells.
    Carcinogenesis. 2015 May;36(5):553-63 PMID: 25784376
  42. Epidemiology of stomach cancer.
    Methods Mol Biol. 2009;472:467-77 PMID: 19107449
  43. Screening for gastric cancer in Asia: current evidence and practice.
    Lancet Oncol. 2008 Mar;9(3):279-87 PMID: 18308253
  44. DNA and histone methylation in gastric carcinogenesis.
    World J Gastroenterol. 2013 Feb 28;19(8):1182-92 PMID: 23482412
  45. Premature of chromosome condensation in a ts DNA- mutant of BHK cells.
    Cell. 1978 Oct;15(2):475-83 PMID: 719750
  46. SVEP1 promoter regulation by methylation of CpG sites.
    Gene. 2011 Dec 15;490(1-2):6-14 PMID: 21963386
  47. p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail.
    Cancer Res. 1994 Sep 1;54(17):4750-5 PMID: 8062274
  48. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus.
    Nature. 1993 Oct 14;365(6447):661-3 PMID: 8413630
  49. Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.
    Biomed Res Int. 2014;2014:378358 PMID: 25197641
Article Info
Journal
International journal of clinical and experimental pathology
Abbr.
Int J Clin Exp Pathol
ISSN
1936-2625
Published
2015-00-00
Epub
2015-00-01
Pages
14257-69
Language
English
Region
United States
NLM ID
101480565
PMCID
PMC4713528
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2