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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
April-2017 Volume 50 Issue 4

Full Size Image

Cover Legend PDF

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-2017 Volume 50 Issue 4

Full Size Image

Cover Legend PDF

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

Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells

  • Authors:
    • Young Il Kim
    • Seung-Won Park
    • Hye Shin Kwon
    • Hyung-Seok Yang
    • Sun Young Cho
    • Young Jin Kim
    • Hee Joo Lee
  • View Affiliations / Copyright

    Affiliations: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea, Department of Biotechnology, Catholic University of Daegu, Daegu 38430, Republic of Korea, Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
  • Pages: 1403-1412
    |
    Published online on: March 2, 2017
       https://doi.org/10.3892/ijo.2017.3895
  • 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 inhibin-α gene was identified as a tumor suppressor gene in the gonads and adrenal glands by functional studies using knockout mice. Methylation of CpG sites within the regulatory regions of tumor suppressor gene is frequently associated with their transcriptional silencing. We investigated epigenetic modifications, changes in loss of heterozygosity (LOH), and mutation of the inhibin-α gene, and regulation of transcriptional expression in response to inhibitors of DNA methylation (5-aza-2'-deoxycytidine, 5-AzaC) in human lymphoid (Jurkat, Molt-4, Raji, and IM-9) and myeloid (HL-60, Kasumi-1, and K562) leukemia cells. The inhibin-α promoter was hypermethylated in lymphoid (Molt-4 and Raji) and myeloid (HL-60 and Kasumi-1) leukemia cells. Inhibin-α gene mutations differed significantly between lymphoid (heterozygote) and myeloid (homozygote) leukemia cells. LOH in the inhibin-α gene was detected in lymphoid and myeloid leukemia cells, with the exception of Jurkat cells. Treatment with 5-AzaC, a demethylating agent, resulted in increased inhibin-α mRNA and protein levels in most of the cell lines. Also, 5-AzaC treatment inhibited cell proliferation and induced apoptosis. Taken together, our results reveal that the inhibin-α gene is transcriptionally silenced in human leukemia cells and that reactivation is suppressed by a demethylating agent. In addition, mutations in, and expression levels of, the inhibin-α gene differed between human lymphoid and myeloid leukemia cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Antequera F, Boyes J and Bird A: High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell. 62:503–514. 1990. View Article : Google Scholar : PubMed/NCBI

2 

Esteller M: CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future. Oncogene. 21:5427–5440. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Okano M, Xie S and Li E: Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 19:219–220. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J and Wolffe AP: Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 19:187–191. 1998. View Article : Google Scholar : PubMed/NCBI

5 

Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN and Bird A: Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 393:386–389. 1998. View Article : Google Scholar : PubMed/NCBI

6 

van der Ploeg LH and Flavell RA: DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. Cell. 19:947–958. 1980. View Article : Google Scholar : PubMed/NCBI

7 

Lichtenstein M, Keini G, Cedar H and Bergman Y: B cell-specific demethylation: A novel role for the intronic κ chain enhancer sequence. Cell. 76:913–923. 1994. View Article : Google Scholar : PubMed/NCBI

8 

Lübbert M, Miller CW and Koef fler HP: Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation. Blood. 78:345–356. 1991.PubMed/NCBI

9 

Felgner J, Kreipe H, Heidorn K, Jaquet K, Heuss R, Zschunke F, Radzun HJ and Parwaresch MR: Lineage-specific methylation of the c-fms gene in blood cells and macrophages. Leukemia. 6:420–425. 1992.PubMed/NCBI

10 

Baylin SB, Herman JG, Graff JR, Vertino PM and Issa JP: Alterations in DNA methylation: A fundamental aspect of neoplasia. Adv Cancer Res. 72:141–196. 1998. View Article : Google Scholar

11 

Toyooka S, Carbone M, Toyooka KO, Bocchetta M, Shivapurkar N, Minna JD and Gazdar AF: Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells. Oncogene. 21:4340–4344. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Tsai CN, Tsai CL, Tse KP, Chang HY and Chang YS: The Epstein- Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci USA. 99:10084–10089. 2002. View Article : Google Scholar

13 

Mathews LS: Activin receptors and cellular signaling by the receptor serine kinase family. Endocr Rev. 15:310–325. 1994. View Article : Google Scholar : PubMed/NCBI

14 

Mather JP, Moore A and Li RH: Activins, inhibins, and follistatins: Further thoughts on a growing family of regulators. Proc Soc Exp Biol Med. 215:209–222. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Risbridger GP, Schmitt JF and Robertson DM: Activins and inhibins in endocrine and other tumors. Endocr Rev. 22:836–858. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Matzuk MM, Finegold MJ, Su JG, Hsueh AJ and Bradley A: α-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature. 360:313–319. 1992. View Article : Google Scholar : PubMed/NCBI

17 

Matzuk MM and Bradley A: Identification and analysis of tumor suppressor genes using transgenic mouse models. Semin Cancer Biol. 5:37–45. 1994.PubMed/NCBI

18 

Schmitt JF, Millar DS, Pedersen JS, Clark SL, Venter DJ, Frydenberg M, Molloy PL and Risbridger GP: Hypermethylation of the inhibin α-subunit gene in prostate carcinoma. Mol Endocrinol. 16:213–220. 2002.PubMed/NCBI

19 

Kim YI, Shim J, Kim BH, Lee SJ, Lee HK, Cho C and Cho BN: Transcriptional silencing of the inhibin-α gene in human gastric carcinoma cells. Int J Oncol. 41:690–700. 2012.PubMed/NCBI

20 

Balanathan P, Ball EM, Wang H, Harris SE, Shelling AN and Risbridger GP: Epigenetic regulation of inhibin α-subunit gene in prostate cancer cell lines. J Mol Endocrinol. 32:55–67. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Chatterton Z, Burke D, Emslie KR, Craig JM, Ng J, Ashley DM, Mechinaud F, Saffery R and Wong NC: Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia. Clin Chem. 60:995–1003. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Liu P, Shen JK, Xu J, Trahan CA, Hornicek FJ and Duan Z: Aberrant DNA methylations in chondrosarcoma. Epigenomics. 8:1519–1525. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Clark SJ, Harrison J, Paul CL and Frommer M: High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 22:2990–2997. 1994. View Article : Google Scholar : PubMed/NCBI

24 

Sundblad V, Chiauzzi VA, Andreone L, Campo S, Charreau EH and Dain L: Controversial role of inhibin α-subunit gene in the aetiology of premature ovarian failure. Hum Reprod. 21:1154–1160. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Kuchler RJ: Development of animal cell populations in vitro. Biochemical Methods in Cell Culture and Virology. Kuchler RJ: Dowden, Hutchinson and Ross Inc. Press; Stroudsburg, PA: pp. 90–113. 1977

26 

Wei QX, Claus R, Hielscher T, Mertens D, Raval A, Oakes CC, Tanner SM, de la Chapelle A, Byrd JC, Stilgenbauer S, et al: Germline allele-specific expression of DAPK1 in chronic lymphocytic leukemia. PLoS One. 8:e552612013. View Article : Google Scholar : PubMed/NCBI

27 

Alers JC, Rochat J, Krijtenburg PJ, Hop WC, Kranse R, Rosenberg C, Tanke HJ, Schröder FH and van Dekken H: Identification of genetic markers for prostatic cancer progression. Lab Invest. 80:931–942. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Suarez BK, Lin J, Burmester JK, Broman KW, Weber JL, Banerjee TK, Goddard KA, Witte JS, Elston RC and Catalona WJ: A genome screen of multiplex sibships with prostate cancer. Am J Hum Genet. 66:933–944. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Longui CA, Lemos-Marini SH, Figueiredo B, Mendonca BB, Castro M, Liberatore R Jr, Watanabe C, Lancellotti CL, Rocha MN, Melo MB, et al: Inhibin α-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers. J Med Genet. 41:354–359. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Zhao J, Richter J, Wagner U, Roth B, Schraml P, Zellweger T, Ackermann D, Schmid U, Moch H, Mihatsch MJ, et al: Chromosomal imbalances in noninvasive papillary bladder neoplasms (pTa). Cancer Res. 59:4658–4661. 1999.PubMed/NCBI

31 

Ransom DT, Barnett TC, Bot J, de Boer B, Metcalf C, Davidson JA and Turbett GR: Loss of heterozygosity on chromosome 2q: Possibly a poor prognostic factor in head and neck cancer. Head Neck. 20:404–410. 1998. View Article : Google Scholar : PubMed/NCBI

32 

Arai M, Yokosuka O, Hirasawa Y, Fukai K, Chiba T, Imazeki F, Kanda T, Yatomi M, Takiguchi Y, Seki N, et al: Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5-Aza-2′-deoxycytidine. Cancer. 106:2514–2525. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Sayar N, Karahan G, Konu O, Bozkurt B, Bozdogan O and Yulug IG: Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer. Clin Epigenetics. 7:1042015. View Article : Google Scholar : PubMed/NCBI

34 

Mikata R, Yokosuka O, Fukai K, Imazeki F, Arai M, Tada M, Kurihara T, Zhang K, Kanda T and Saisho H: Analysis of genes upregulated by the demethylating agent 5-aza-2′-deoxycytidine in gastric cancer cell lines. Int J Cancer. 119:1616–1622. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Bender CM, Pao MM and Jones PA: Inhibition of DNA methylation by 5-aza-2′-deoxycytidine suppresses the growth of human tumor cell lines. Cancer Res. 58:95–101. 1998.PubMed/NCBI

36 

Song SH, Jong HS, Choi HH, Inoue H, Tanabe T, Kim NK and Bang YJ: Transcriptional silencing of Cyclooxygenase-2 by hyper-methylation of the 5′ CpG island in human gastric carcinoma cells. Cancer Res. 61:4628–4635. 2001.PubMed/NCBI

37 

Valdez BC, Li Y, Murray D, Corn P, Champlin RE and Andersson BS: 5-Aza-2′-deoxycytidine sensitizes busulfan- resistant myeloid leukemia cells by regulating expression of genes involved in cell cycle checkpoint and apoptosis. Leuk Res. 34:364–372. 2010. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim YI, Park S, Kwon HS, Yang H, Cho SY, Kim YJ and Lee HJ: Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells. Int J Oncol 50: 1403-1412, 2017.
APA
Kim, Y.I., Park, S., Kwon, H.S., Yang, H., Cho, S.Y., Kim, Y.J., & Lee, H.J. (2017). Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells. International Journal of Oncology, 50, 1403-1412. https://doi.org/10.3892/ijo.2017.3895
MLA
Kim, Y. I., Park, S., Kwon, H. S., Yang, H., Cho, S. Y., Kim, Y. J., Lee, H. J."Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells". International Journal of Oncology 50.4 (2017): 1403-1412.
Chicago
Kim, Y. I., Park, S., Kwon, H. S., Yang, H., Cho, S. Y., Kim, Y. J., Lee, H. J."Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells". International Journal of Oncology 50, no. 4 (2017): 1403-1412. https://doi.org/10.3892/ijo.2017.3895
Copy and paste a formatted citation
x
Spandidos Publications style
Kim YI, Park S, Kwon HS, Yang H, Cho SY, Kim YJ and Lee HJ: Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells. Int J Oncol 50: 1403-1412, 2017.
APA
Kim, Y.I., Park, S., Kwon, H.S., Yang, H., Cho, S.Y., Kim, Y.J., & Lee, H.J. (2017). Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells. International Journal of Oncology, 50, 1403-1412. https://doi.org/10.3892/ijo.2017.3895
MLA
Kim, Y. I., Park, S., Kwon, H. S., Yang, H., Cho, S. Y., Kim, Y. J., Lee, H. J."Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells". International Journal of Oncology 50.4 (2017): 1403-1412.
Chicago
Kim, Y. I., Park, S., Kwon, H. S., Yang, H., Cho, S. Y., Kim, Y. J., Lee, H. J."Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells". International Journal of Oncology 50, no. 4 (2017): 1403-1412. https://doi.org/10.3892/ijo.2017.3895
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