Skip to main content

Advertisement

SpringerLink
Log in

Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of the study is to the determine the profiles of cell cycle genes and a new candidate oncogene of URG4/URGCP which play role in leukemia, establishing the association between the early prognosis of cancer and the quantitation of genetic changes, and bringing a molecular approach to definite diagnosis. In this study, 36 newly diagnosed patients’ with ALL-AML in the range of 0–18 years and six control group patients’ bone marrow samples were included. Total RNA was isolated from samples and then complementary DNA synthesis was performed. The obtained cDNAs have been installed 96 well plates after prepared appropriate mixtures and assessed with LightCycler® 480 Real-Time PCR quantitatively. CHEK1, URG4/URGCP, CCNG1, CCNC, CDC16, KRAS, CDKN2D genes in the T-ALL group; CCND2, ATM, CDK8, CHEK1, TP53, CHEK2, CCNG2, CDK4, CDKN2A, E2F4, CCNC, KRAS genes in the precursor B-ALL group and CCND2, CDK6 genes in the AML group have shown significant increase in mRNA expression level. In the featured role of acute leukemia the regulating signaling pathways of leukemogenesis partially defined, although identification of new genetic markers in acute leukemia subgroups, will allow the development of early diagnostic and new treatment protocols.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Biondi A, Cimino G, Pieters R, Pui CH (2000) Biological and therapeutic aspects of infant leukemia. Blood 96:24–33

    PubMed  CAS  Google Scholar 

  2. Mullighan CG, Goorha S, Radtke I et al (2007) Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446:758–764

    Article  PubMed  CAS  Google Scholar 

  3. Sherr CJ (1996) Cancer cell cycles. Science 274:1672

    Article  PubMed  CAS  Google Scholar 

  4. Clarke MF, Dick JE, Dirks PB et al (2006) Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66:9339–9344

    Article  PubMed  CAS  Google Scholar 

  5. Benekli M, Baer MR, Baumann H et al (2003) Signal transducer and activator of transcription proteins in leukemias. Blood 101:2940–2954

    Article  PubMed  CAS  Google Scholar 

  6. Gesbert F, Griffin JD et al (2000) Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood 96:2269–2276

    PubMed  CAS  Google Scholar 

  7. Satiroglu-Tufan NL, Dodurga Y, Gok D, Cetinkaya A, Feitelson MA (2010) RNA interference-mediated URG4 gene silencing diminishes cyclin D1 mRNA expression in HepG2 cells. Genet Mol Res 9(3):1557–1567

    Article  PubMed  CAS  Google Scholar 

  8. Tufan NL, Lian Z, Liu J et al (2002) Hepatitis Bx antigen stimulates expression of a novel cellular gene, URG4, that promotes hepatocellular growth and survival. Neoplasia 4(4):355–368

    Article  PubMed  CAS  Google Scholar 

  9. Song J, Xie H, Lian Z et al (2006) Enhanced cell survival of gastric cancer cells by a novel gene URG4. Neoplasia 8(12):995–1002

    Article  PubMed  Google Scholar 

  10. Huang J, Zhu B, Lu L et al (2009) The expression of novel gene URG4 in osteosarcoma: correlation with patients prognosis. Pathology 41(2):149–154

    Article  PubMed  CAS  Google Scholar 

  11. Dodurga Y, Avcı CB, Susluer SY, Satıroğlu Tufan NL, Gündüz C (2012) The expression of URGCP gene in prostate cancer cell lines: correlation with rapamycin. Mol Biol Rep. doi:10.1007/s11033-012-1891-6

    Google Scholar 

  12. Shiloh Y, Kastan MB et al (2001) ATM: genome stability, neuronal development, and cancer cross paths. Adv Cancer Res 83:209–254

    Article  PubMed  CAS  Google Scholar 

  13. Lavin MF, Birrell G, Chen P et al (2005) ATM signaling and genomic stability in response to DNA damage. Mutat Res 569(1–2):123–132

    PubMed  CAS  Google Scholar 

  14. Takagaki K, Katsuma S, Kaminishi Y et al (2005) Role of Chk1 and Chk2 in Ara-C-ınduced differentiation of human leukemia K562 cells. Genes Cells 10:97–106

    Article  PubMed  CAS  Google Scholar 

  15. Halicka HD, Ozkaynak MF, Levendoglu-Tugal O et al (2009) DNA damage response as a biomarker in treatment of leukemias. Cell Cycle 8(11):1720–1724

    Article  PubMed  CAS  Google Scholar 

  16. Khanna KK, Keating KE, Kozlov S et al (1998) ATM associates with and phosphorylates p53: mapping the region of ınteraction. Nat Genet 20:398–400

    Article  PubMed  CAS  Google Scholar 

  17. Shafman T, Khanna KK, Kedar P et al (1997) Interaction between ATM protein and c-Abl in response to DNA damage. Nature 387:520–523

    Article  PubMed  CAS  Google Scholar 

  18. Soenen V, Lepelley P, Gyan E et al (2001) Prognostic significance of p16ınk4a ımmunocytochemistry in adult ALL with standard risk karyotype. Leukemia 15:1054–1059

    Article  PubMed  CAS  Google Scholar 

  19. Dalle JH, Fournier M, Nelken B et al (2000) p16INK4a ımmunocytochemical analysis is an ındependent prognostic factor in childhood acute lymphoblastic leukemia. Blood 99:2620–2623

    Article  Google Scholar 

  20. Omura-Minamisawa M, Diccianni MB, Batova A et al (2000) Universal ınactivation of both p16 and p15 but not downstream components is an essential event in the pathogenesis of T-cell acute lymphoblastic leukemia. Clin Cancer Res 6(4):1219–1228

    PubMed  CAS  Google Scholar 

  21. Mittnacht S, Andweınberg RA (1991) G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65:381–393

    Article  PubMed  CAS  Google Scholar 

  22. Chellappan SP, Hiebert S, Mudry JM (1991) The E2F4 transcription factor is a cellular target for the Rb protein. Cell 65:1053–1062

    Article  PubMed  CAS  Google Scholar 

  23. Paulsson K, Horvat A, Strombeck B (2008) Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhoodacute lymphoblastic leukemia. Genes Chromosomes Cancer 47:26–33

    Article  PubMed  CAS  Google Scholar 

  24. Katona RL, Loyer P, Roby SK, Lahti JM (2007) Two ısoforms of the human cyclin C gene are expressed differentially suggesting that they may have distinct functions. Acta Biol Hung 58:133–137

    Article  PubMed  CAS  Google Scholar 

  25. Ohata N, Ito S, Yoshida A (2006) Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: ınvolvement of cyclin C in osteosarcoma. Int J Mol Med 18(6):1153–1158

    PubMed  CAS  Google Scholar 

  26. Zhang ZX, Cao LZ, Huang Q (2008) Detection of human cyclin C gene expression in childhood acute lymphocytic leukemia using real-time fluorescence quantitative PCR. Zhongguo Dang Dai Er Ke Za Zhi 10:14–16

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study is supported by Ege University Research Projects (APAK) within the scope of the project numbered 2009-TIP-34.

Author information

Authors and Affiliations

  1. Department of Medical Biology, School of Medicine, Pamukkale University, Kınıklı Kampüsü Morfoloji Binasi Kat:3, Kınıklı/Denizli, Turkey

    Yavuz Dodurga

  2. Department of Pediatric Hematology and Oncology, Dr. Behcet Uz Hospital, Izmir, Turkey

    Yeşim Oymak & Canan Vergin

  3. Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey

    Cumhur Gündüz, Çığır Biray Avci & Nejat Topçuoğlu

  4. Department of Medical Genetics, School of Medicine, Pamukkale University, Denizli, Turkey

    N. Lale Satıroglu-Tufan

  5. Department of Pediatric Oncology, School of Medicine, Ege University, Izmir, Turkey

    Nazan Çetingül

Authors
  1. Yavuz Dodurga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yeşim Oymak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cumhur Gündüz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Lale Satıroglu-Tufan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Canan Vergin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nazan Çetingül
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Çığır Biray Avci
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nejat Topçuoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yavuz Dodurga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dodurga, Y., Oymak, Y., Gündüz, C. et al. Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia. Mol Biol Rep 40, 3043–3048 (2013). https://doi.org/10.1007/s11033-012-2378-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2378-1

Keywords

Search

Navigation