Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2019 Volume 19 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2019 Volume 19 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma

  • Authors:
    • Lei Liu
    • Shaowei Zhang
    • Xinbo Liu
    • Junfeng Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
  • Pages: 3273-3282
    |
    Published online on: February 19, 2019
       https://doi.org/10.3892/mmr.2019.9971
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The human protein tyrosine phosphatase, non‑receptor type 6 (PTPN6) gene is located on chromosome 12p13 and encodes an Mr 68,000 non‑receptor type protein‑tyrosine phosphatase. The PTPN6 gene has been considered as a candidate tumor suppressor in hematological and solid malignancies, and promoter methylation may be an epigenetic modification silencing its expression. However, the detailed role of PTPN6 and its promoter methylation status in the pathogenesis of esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The aim of the present study was to investigate PTPN6 expression in ESCC tissues and esophageal cancer cell lines, detect the effect of CpG hypermethylation on the activity of PTPN6, and additionally elucidate the role and prognostic significance of PTPN6 in ESCC tumorigenesis and progression. The expression of PTPN6 was identified to be significantly downregulated in esophageal cancer cell lines and ESCC tissues. Marked upregulation of PTPN6 was detected in 5‑aza‑2'‑deoxycytidine‑treated esophageal cancer cells, and frequent hypermethylation of the CpG sites within the P2 promoter (P2) was detected in ESCC tissues and esophageal cancer cell lines. The expression and methylation status of PTPN6 was associated with tumor node metastasis stage, pathological differentiation and lymph node metastasis in patients with ESCC. Aberrant hypermethylation of the P2 exhibited marked tumor specificity and was identified to be associated with the expression level of PTPN6. Downregulation and hypermethylation of PTPN6 were identified to be associated with poor ESCC patient survival. Furthermore, upregulation of PTPN6 inhibited the proliferation and invasion of esophageal cancer cells in vitro. The results of the present study suggest that PTPN6 may serve as a tumor suppressor in ESCC, and it may serve as a potential target for antitumor therapy.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Lambert R and Hainaut P: The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer. Best Pract Res Clin Gastroenterol. 21:921–945. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Guohong Z, Min S, Duenmei W, Songnian H, Min L, Jinsong L, Hongbin L, Feng Z, Dongping T, Heling Y, et al: Genetic heterogeneity of oesophageal cancer in high-incidence areas of southern and northern China. PLoS One. 5:e96682010. View Article : Google Scholar : PubMed/NCBI

4 

Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Meeusen B and Janssens V: Tumor suppressive protein phosphatases in human cancer: Emerging targets for therapeutic intervention and tumor stratification. Int J Biochem Cell Biol. 96:98–134. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Elson A: Stepping out of the shadows: Oncogenic and tumor-promoting protein tyrosine phosphatases. Int J Biochem Cell Biol. 96:135–147. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Tonks NK: Protein tyrosine phosphatases-from housekeeping enzymes to master regulators of signal transduction. FEBS J. 280:346–378. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Kleppe M, Soulier J, Asnafi V, Mentens N, Hornakova T, Knoops L, Constantinescu S, Sigaux F, Meijerink JP, Vandenberghe P, et al: PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. Blood. 117:7090–7098. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Plutzky J, Neel BG, Rosenberg RD, Eddy RL, Byers MG, Jani-Sait S and Shows TB: Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6). Genomics. 13:869–872. 1992. View Article : Google Scholar : PubMed/NCBI

10 

Oka T, Yoshino T, Hayashi K, Ohara N, Nakanishi T, Yamaai Y, Hiraki A, Sogawa CA, Kondo E, Teramoto N, et al: Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias: Combination analysis with cDNA expression array and tissue microarray. Am J Pathol. 159:1495–1505. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Chim CS, Fung TK, Cheung WC, Liang R and Kwong YL: SOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway. Blood. 103:4630–4635. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Amin HM, Hoshino K, Yang H, Lin Q, Lai R and Garcia-Manero G: Decreased expression level of SH2 domain-containing protein tyrosine phosphatase-1 (Shp1) is associated with progression of chronic myeloid leukaemia. J Pathol. 212:402–410. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Challouf S, Ziadi S, Zaghdoudi R, Ksiaa F, Ben Gacem R and Trimeche M: Patterns of aberrant DNA hypermethylation in nasopharyngeal carcinoma in Tunisian patients. Clin Chim Acta. 413:795–802. 2010. View Article : Google Scholar

14 

Hachana M, Trimeche M, Ziadi S, Amara K and Korbi S: Evidence for a role of the Simian Virus 40 in human breast carcinomas. Breast Cancer Res Treat. 113:43–58. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Banville D, Stocco R and Shen SH: Human protein tyrosine phosphatase 1C (PTPN6) gene structure: Alternate promoter usage and exon skipping generate multiple transcripts. Genomics. 27:165–173. 1995. View Article : Google Scholar : PubMed/NCBI

16 

Tsui FW, Martin A, Wang J and Tsui HW: Investigations into the regulation and function of the SH2 domain-containing protein-tyrosine phosphatase, SHP-1. Immunol Res. 35:127–136. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Yamasaki M, Miyata H, Miyazaki Y, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M and Doki Y: Evaluation of the nodal status in the 7th edition of the UICC-TNM classification for esophageal squamous cell carcinoma: Proposed modifications for improved survival stratification: Impact of lymph node metastases on overall survival after esophagectomy. Ann Surg Oncol. 21:2850–2856. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Warnecke PM and Bestor TH: Cytosine methylation and human cancer. Curr Opin Oncol. 12:68–73. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Parris TZ, Kovács A, Hajizadeh S, Nemes S, Semaan M, Levin M, Karlsson P and Helou K: Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas. Oncogenesis. 3:e952014. View Article : Google Scholar : PubMed/NCBI

21 

Vasiljević N, Scibior-Bentkowska D, Brentnall AR, Cuzick J and Lorincz AT: Credentialing of DNA methylation assays for human genes as diagnostic biomarkers of cervical intraepithelial neoplasia in high-risk HPV positive women. Gynecol Oncol. 132:709–714. 2014. View Article : Google Scholar : PubMed/NCBI

22 

El-Osta A, Baker EK and Wolffe AP: Profiling methyl-CpG specific determinants on transcriptionally silent chromatin. Mol Biol Rep. 28:209–215. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Oka T, Ouchida M, Koyama M, Ogama Y, Takada S, Nakatani Y, Tanaka T, Yoshino T, Hayashi K, Ohara N, et al: Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas. Cancer Res. 62:6390–6394. 2002.PubMed/NCBI

24 

Chim CS, Wong KY, Loong F and Srivastava G: SOCS1 and SHP1 hypermethylation in mantle cell lymphoma and follicular lymphoma: Implications for epigenetic activation of the Jak/STAT pathway. Leukemia. 18:356–358. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Sheng Y, Wang H, Liu D and Zhang C, Deng Y, Yang F, Zhang T and Zhang C: Methylation of tumor suppressor gene CDH13 and SHP1 promoters and their epigenetic regulation by the UHRF1/PRMT5 complex in endometrial carcinoma. Gynecol Oncol. 140:145–151. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Zhang MY, Fung TK, Chen FY and Chim CS: Methylation profiling of SOCS1, SOCS2, SOCS3, CISH and SHP1 in Philadelphia-negative myeloproliferative neoplasm. J Cell Mol Med. 17:1282–1290. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Han Y, Amin HM, Frantz C, Franko B, Lee J, Lin Q and Lai R: Restoration of shp1 expression by 5-AZA-2′-deoxycytidine is associated with downregulation of JAK3/STAT3 signaling in ALK-positive anaplastic large cell lymphoma. Leukemia. 20:1602–1609. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Niwa Y, Kanda H, Shikauchi Y, Saiura A, Matsubara K, Kitagawa T, Yamamoto J, Kubo T and Yoshikawa H: Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene. 24:6406–6417. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu L, Zhang S, Liu X and Liu J: Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma. Mol Med Rep 19: 3273-3282, 2019.
APA
Liu, L., Zhang, S., Liu, X., & Liu, J. (2019). Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma. Molecular Medicine Reports, 19, 3273-3282. https://doi.org/10.3892/mmr.2019.9971
MLA
Liu, L., Zhang, S., Liu, X., Liu, J."Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma". Molecular Medicine Reports 19.4 (2019): 3273-3282.
Chicago
Liu, L., Zhang, S., Liu, X., Liu, J."Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma". Molecular Medicine Reports 19, no. 4 (2019): 3273-3282. https://doi.org/10.3892/mmr.2019.9971
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Zhang S, Liu X and Liu J: Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma. Mol Med Rep 19: 3273-3282, 2019.
APA
Liu, L., Zhang, S., Liu, X., & Liu, J. (2019). Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma. Molecular Medicine Reports, 19, 3273-3282. https://doi.org/10.3892/mmr.2019.9971
MLA
Liu, L., Zhang, S., Liu, X., Liu, J."Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma". Molecular Medicine Reports 19.4 (2019): 3273-3282.
Chicago
Liu, L., Zhang, S., Liu, X., Liu, J."Aberrant promoter 2 methylation‑mediated downregulation of protein tyrosine phosphatase, non‑receptor type 6, is associated with progression of esophageal squamous cell carcinoma". Molecular Medicine Reports 19, no. 4 (2019): 3273-3282. https://doi.org/10.3892/mmr.2019.9971
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team