Advertisement

Tumor Biology

, Volume 31, Issue 6, pp 597–604 | Cite as

CDC25A gene 263C/T, -350C/T, and -51C/G polymorphisms in breast carcinoma

  • Isik Didem Karagoz
  • Mehmet Ozaslan
  • Beyhan Cengiz
  • Mehmet Emin Kalender
  • Ibrahim Halil Kilic
  • Serdar Oztuzcu
  • Bulent Gogebakan
  • Abdullah Tuncay Demiryurek
Research Article

Abstract

The family of cell division cycle 25 (CDC25) phosphatase is one of the important regulators of the cell cycle progression. In mammalian cells, three isoforms have been identified: CDC25A, CDC25B, and CDC25C. CDC25A is required to enter S time, and the overexpression of this phosphatase accelerates the entrance to S time. CDC25A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability. We aimed to investigate, for the first time, the frequency of human CDC25A gene SNPs in metastatic and non-metastatic breast cancer. Total number of 281 eligible patients with histologically confirmed incident of breast cancer and 137 cancer-free controls were included. The detection of CDC25A gene polymorphisms was achieved with real-time polymerase chain reaction and restriction fragment length polymorphism techniques. We found that the 263C/T polymorphism was significantly associated with breast cancer and risk of metastasis. The -350C/T polymorphism in the promoter region of CDC25A gene was found to associate with neither breast cancer nor metastasis. The other promoter polymorphism -51C/G in the CDC25A gene associated with breast cancer but not associated with metastasis. These data suggest that 263C/T and -51C/G polymorphisms of CDC25A gene could be candidate markers for earlier diagnosis and targets for breast cancer therapy.

Keywords

CDC25A Breast cancer Cell cycle Polymorphism 

Notes

Acknowledgments

The authors give their thanks to Dr. Celalettin Camci in the Department of Oncology, University of Gaziantep, in Gaziantep Turkey, for his valuable advise and cooperation in this research work.

Role of the funding source

This study was funded by the University of Gaziantep, Scientific Research Projects (GAUNBAP FEF 09.06, Gaziantep, Turkey).

References

  1. 1.
    Gürtunç E: Meme Kanserli Hastalarda CYP19 Geni Kodon 39 Trp/Arg Polimorfizminin ve Genotip Dağılımının Araştırılması. Yüksek Lisans Tezi. Çukurova Üniv Sağlık Bilimleri Ens Tıbbi Biyoloji ABD 2007.Google Scholar
  2. 2.
    Yıldız Y: Meme Kanserli Hastalarda TNF ile İlişkili Apoptoz Uyarıcı Ligand ve Bcl-2 ile İlişkili X-Protein Gen Polimorfizmlerinin Araştırılması. Yüksek Lisans Tezi. İstanbul Üniv Sağlık Bilimleri Ens Moleküler Tıp ABD 2008.Google Scholar
  3. 3.
    Ma H, Hu Z, Zhai X, Wang S, Wang X, Qin J, et al. Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control analysis in a Chinese population. Cancer Lett. 2006;240:261–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Hossfeld DK, Sherman CD, Love RR, Bosch FX: Klinik Onkoloji. Uluslararası Kanserle Savaş Birliği 1992; 5th edition, p 25.Google Scholar
  5. 5.
    Boutros R, Lobjois V, Ducommun B. CDC25 phosphatases in cancer cells: key players? good targets? Nat Rev Cancer. 2007;7:495–507.CrossRefPubMedGoogle Scholar
  6. 6.
    Cangi MG, Cukor B, Soung P, Signoretti S, Moreira Jr G, Ranashinge M, et al. Role of the CDC25A phosphatase in human breast cancer. J Clin Invest. 2000;106:753–61.CrossRefPubMedGoogle Scholar
  7. 7.
    Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H, et al. CDC25A is a novel phosphatase functioning early in the cell cycle. EMBO J. 1994;13:1549–56.PubMedGoogle Scholar
  8. 8.
    Hoffmann I, Draetta G, Karsenti E. Activation of the phosphatase activity of human CDC25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J. 1994;13:4302–10.PubMedGoogle Scholar
  9. 9.
    Boutros R, Dozier C, Ducommun B. The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol. 2006;18:185–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Molinari M, Mercurio C, Dominguez J, Goubin F, Draetta GF. Human CDC25A inactivation in response to S time inhibition and its role in preventing premature mitosis. EMBO Rep. 2000;1:71–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Gasparotto D, Maestro R, Piccinin S, Vukosavljevic T, Barzan L, Sulfaro S, et al. Overexpression of CDC25A and CDC25B in head and neck cancers. Cancer Res. 1997;57:2366–8.PubMedGoogle Scholar
  12. 12.
    Hernandez S, Hernandez L, Bea S, Cazorla M, Fernandez PL, Nadal A, et al. CDC25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin’s lymphomas. Cancer Res. 1998;58:1762–7.PubMedGoogle Scholar
  13. 13.
    Kudo Y, Yasui W, Ue T, Yamamoto S, Yokozaki H, Nikai H, et al. Overexpression of cyclin-dependent kinase-activating CDC25B phosphatase in human gastric carcinomas. Jpn J Cancer Res. 1997;88:947–52.PubMedGoogle Scholar
  14. 14.
    Wu W, Fan Y, Kemp B, Walsh G, Mao L. Overexpression of CDC25A and CDC25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc. Cancer Res. 1998;58:4082–5.PubMedGoogle Scholar
  15. 15.
    Moreira Jr G, Colleoni GWB, Cangi MG, Murphy M, Sherburne B, et al. Reciprocal CDC25A and p27 expression in B-cell non-Hodgkin lymphomas. Diagn Mol Pathol. 2003;12(3):128–32.Google Scholar
  16. 16.
    Hernandez S, Bessa X, Bea S, Hernandez L, Nadal A, Mallofre C, et al. Differential expression of CDC25 cell-cycle-activating phosphatases in human colorectal carcinoma. Lab Invest. 2001;81:465–73.PubMedGoogle Scholar
  17. 17.
    Ray D, Kiyokama H. CDC25A phosphatase: a rate-limiting oncogene that determines genomic stability. Cancer Res. 2008;68(5):1251–3.CrossRefPubMedGoogle Scholar
  18. 18.
    Cangi MG, Piccinin S, Pecciarini L, Talarico A, Cin ED, Grassi S, et al. Constitutive overexpression of CDC25A in primary human mammary epithelial cells results in both defective DNA damage response and chromosomal breaks at fragile sites. Int J Cancer. 2008;123:1466–71.CrossRefPubMedGoogle Scholar
  19. 19.
  20. 20.
    Cozma D, Lukes L, Rouse J, Qiu TH, Liu ET, Hunter KW. A bioinformatics-based strategy identifies c-Myc and CDC25A as candidates for the Apmt mammary tumour latency modifiers. Genome Res. 2002;12:969–75.CrossRefPubMedGoogle Scholar
  21. 21.
    Ito Y, Yoshida H, Uruno T, Takamura Y, Miya A, Kuma K, et al. Expression of CDC25A and CDC25B phosphatase in breast carcinoma. Breast Cancer. 2004;11:295–300.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Isik Didem Karagoz
    • 1
  • Mehmet Ozaslan
    • 1
  • Beyhan Cengiz
    • 2
  • Mehmet Emin Kalender
    • 5
  • Ibrahim Halil Kilic
    • 1
  • Serdar Oztuzcu
    • 3
  • Bulent Gogebakan
    • 3
  • Abdullah Tuncay Demiryurek
    • 4
  1. 1.Department of Biological SciencesUniversity of GaziantepGaziantepTurkey
  2. 2.Department of PhysiologyUniversity of GaziantepGaziantepTurkey
  3. 3.Department of Medical Biology and GeneticsUniversity of GaziantepGaziantepTurkey
  4. 4.Department of PharmacologyUniversity of GaziantepGaziantepTurkey
  5. 5.Department of Medical Oncology, Gaziantep Oncology HospitalUniversity of GaziantepGaziantepTurkey

Personalised recommendations