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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2016 Volume 12 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
October-2016 Volume 12 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

Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma

  • Authors:
    • Gaia Gozzi
    • Sonia T. Chelbi
    • Paola Manni
    • Loredana Alberti
    • Sergio Fonda
    • Sara Saponaro
    • Luca Fabbiani
    • Francesco Rivasi
    • Jean Benhattar
    • Lorena Losi
  • View Affiliations / Copyright

    Affiliations: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I‑41124 Modena, Italy, University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland, Department of Diagnostic Medicine, Clinic and Public Health, University of Modena and Reggio Emilia, I‑41124 Modena, Italy
  • Pages: 2811-2819
    |
    Published online on: August 16, 2016
       https://doi.org/10.3892/ol.2016.5019
  • 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

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Auersperg N: Ovarian surface epithelium as a source of ovarian cancers: Unwarranted speculation or evidence-based hypothesis? Gynecol Oncol. 130:246–251. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Kurman RJ and Shih IeM: The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol. 34:433–443. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Kurman RJ, Carcangiu ML, Herrington CS and Young RH: WHO Classification of Tumours of Female Reproductive Organs (4th). IARC. Lyon: 2014.

4 

Gloss BS and Samimi G: Epigenetic biomarkers in epithelial ovarian cancer. Cancer Lett. 342:257–263. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Showell C, Binder O and Conlon FL: T-box genes in early embryogenesis. Dev Dyn. 229:201–218. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Takashima Y and Suzuki A: Regulation of organogenesis and stem cell properties by T-box transcription factors. Cell Mol Life Sci. 70:3929–3945. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Dorfman DM, Hwang ES, Shahsafaei A and Glimcher LH: T-bet, a T-cell-associated transcription factor, is expressed in a subset of B-cell lymphoproliferative disorders. Am J Clin Pathol. 122:292–297. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Dorfman DM, Hwang ES, Shahsafaei A and Glimcher LH: T-bet, a T cell-associated transcription factor, is expressed in Hodgkin's lymphoma. Hum Pathol. 36:10–15. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Ito A, Asamoto M, Hokaiwado N, Takahashi S and Shirai T: Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. Cancer Lett. 219:105–112. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Rowley M, Grothey E and Couch FJ: The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. J Mammary Gland Biol Neoplasia. 9:109–118. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Kispert A, Herrmann BG, Leptin M and Reuter R: Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium and Locusta. Genes Dev. 8:2137–2150. 1994. View Article : Google Scholar : PubMed/NCBI

12 

Vidricaire G, Jardine K and McBurney MW: Expression of the Brachyury gene during mesoderm development in differentiating embryonal carcinoma cell cultures. Development. 120:115–122. 1994.PubMed/NCBI

13 

Farin HF, Bussen M, Schmidt MK, Singh MK, Schuster-Gossler K and Kispert A: Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J Biol Chem. 282:25748–25759. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Buscarlet M and Stifani S: The ‘Marx’ of Groucho on development and disease. Trends Cell Biol. 17:353–361. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Kron K, Pethe V, Briollais L, Sadikovic B, Ozcelik H, Sunderji A, Venkateswaran V, Pinthus J, Fleshner N, van der Kwast T and Bapat B: Discovery of novel hypermethylated genes in prostate cancer using genomic CpG island microarrays. PLoS One. 4:e48302009. View Article : Google Scholar : PubMed/NCBI

16 

Kron K, Liu L, Trudel D, Pethe V, Trachtenberg J, Fleshner N, Bapat B and van der Kwast T: Correlation of ERG expression and DNA methylation biomarkers with adverse clinicopathologic features of prostate cancer. Clin Cancer Res. 18:2896–2904. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Prat J: FIGO committee on gynecologic oncology: Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 124:1–5. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Silverberg SG: Histopathologic grading of ovarian carcinoma: A review and proposal. Int J Gynecol Pathol. 19:7–15. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM and Silva EG: Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol. 28:496–504. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Chelbi ST, Doridot L, Mondon F, Dussour C, Rebourcet R, Busato F, Gascoin-Lachambre G, Barbaux S, Rigourd V, Mignot TM, et al: Combination of promoter hypomethylation and PDX1 overexpression leads to TBX15 decrease in vascular IUGR placentas. Epigenetics. 6:247–255. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Bock C, Reither S, Mikeska T, Paulsen M, Walter J and Lengauer T: BiQ analyzer: Visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics. 21:4067–4068. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Losi L, Baisse B, Bouzourene H and Benhattar J: Evolution of intratumoral genetic heterogeneity during colorectal cancer progression. Carcinogenesis. 26:916–922. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Moelans CB, de Groot JS, Pan X, van der Wall E and van Diest PJ: Clonal intratumor heterogeneity of promoter hypermethylation in breast cancer by MS-MLPA. Mod Pathol. 27:869–874. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Woloszynska-Read A, Mhawech-Fauceglia P, Yu J, Odunsi K and Karpf AR: Intertumor and intratumor NY-ESO-1 expression heterogeneity is associated with promoter-specific and global DNA methylation status in ovarian cancer. Clin Cancer Res. 14:3283–3290. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Imajyo I, Sugiura T, Kobayashi Y, Shimoda M, Ishii K, Akimoto N, Yoshihama N, Kobayashi I and Mori Y: T-box transcription factor Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma. Int J Oncol. 41:1985–1995. 2012.PubMed/NCBI

26 

Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 133:704–715. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Blick T, Hugo H, Widodo E, Waltham M, Pinto C, Mani SA, Weinberg RA, Neve RM, Lenburg ME and Thompson EW: Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24 (lo/−) stem cell phenotype in human breast cancer. J Mammary Gland Biol Neoplasia. 15:235–252. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Sarkar D, Shields B, Davies ML, Müller J and Wakeman JA: BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells. Int J Cancer. 130:328–337. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gozzi G, Chelbi ST, Manni P, Alberti L, Fonda S, Saponaro S, Fabbiani L, Rivasi F, Benhattar J, Losi L, Losi L, et al: Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma. Oncol Lett 12: 2811-2819, 2016.
APA
Gozzi, G., Chelbi, S.T., Manni, P., Alberti, L., Fonda, S., Saponaro, S. ... Losi, L. (2016). Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma. Oncology Letters, 12, 2811-2819. https://doi.org/10.3892/ol.2016.5019
MLA
Gozzi, G., Chelbi, S. T., Manni, P., Alberti, L., Fonda, S., Saponaro, S., Fabbiani, L., Rivasi, F., Benhattar, J., Losi, L."Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma". Oncology Letters 12.4 (2016): 2811-2819.
Chicago
Gozzi, G., Chelbi, S. T., Manni, P., Alberti, L., Fonda, S., Saponaro, S., Fabbiani, L., Rivasi, F., Benhattar, J., Losi, L."Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma". Oncology Letters 12, no. 4 (2016): 2811-2819. https://doi.org/10.3892/ol.2016.5019
Copy and paste a formatted citation
x
Spandidos Publications style
Gozzi G, Chelbi ST, Manni P, Alberti L, Fonda S, Saponaro S, Fabbiani L, Rivasi F, Benhattar J, Losi L, Losi L, et al: Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma. Oncol Lett 12: 2811-2819, 2016.
APA
Gozzi, G., Chelbi, S.T., Manni, P., Alberti, L., Fonda, S., Saponaro, S. ... Losi, L. (2016). Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma. Oncology Letters, 12, 2811-2819. https://doi.org/10.3892/ol.2016.5019
MLA
Gozzi, G., Chelbi, S. T., Manni, P., Alberti, L., Fonda, S., Saponaro, S., Fabbiani, L., Rivasi, F., Benhattar, J., Losi, L."Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma". Oncology Letters 12.4 (2016): 2811-2819.
Chicago
Gozzi, G., Chelbi, S. T., Manni, P., Alberti, L., Fonda, S., Saponaro, S., Fabbiani, L., Rivasi, F., Benhattar, J., Losi, L."Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma". Oncology Letters 12, no. 4 (2016): 2811-2819. https://doi.org/10.3892/ol.2016.5019
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