Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지
DOI QR코드

DOI QR Code

DNA-Damage Inducible 1 is a Property of Human Non-Small Cell Lung Cancer

  • Lee, Ji-Yeon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine) ;
  • Kang, Eun-Sil (Department of Internal Medicine, Yonsei University Health System, Yonsei University College of Medicine) ;
  • Lim, Beom-Jin (Department of Pathology, Yonsei University Health System, Yonsei University College of Medicine) ;
  • Chang, Yoon-Soo (Department of Internal Medicine, Yonsei University Health System, Yonsei University College of Medicine) ;
  • Kim, Se-Kyu (Department of Internal Medicine, Yonsei University Health System, Yonsei University College of Medicine)
  • Received : 2011.11.03
  • Accepted : 2011.12.21
  • Published : 2012.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Background: DNA damage-inducible 1 (Ddi1), one of the ubiquitin-like and ubiquitin-associated family of proteins, may function in the regulation of the ubiquitin-proteasome pathway, which has been validated as a target for antineoplastic therapy. We investigated Ddi1 expression in human lung cancer tissues and evaluated the relationship of this expression pattern with clinicopathological factors in patients with non-small-cell lung cancer (NSCLC). Methods: Ddi1 expression was examined by immunohistochemistry in tumor tissues from 97 patients with stage I NSCLC, who had undergone curative surgical resection at two tertiary referral hospitals from 1993~2004. None of the patients received preoperative chemotherapy and/or radiation therapy. Results: Thirty-nine (40.2%) of the 97 cases were positive for Ddi1. Ddi1 expression was dominantly seen in cytoplasm rather than in the nuclei of cancer cells in all histological types, whereas adjacent nontumoral lung tissue showed negative Ddi1 staining in most cases. Ddi1 expression tended to increase in well-differentiated tumors but without statistical significance. Positive Ddi1 expression was associated with a tendency for better disease-free survival and disease-specific survival, although the difference was not significant. Conclusion: Ddi1 expression is a property of NSCLC. Because Ddi1 could be a potential target for cancer therapy, more research is needed to evaluate its role in NSCLC.

Keywords

References

  1. Brundage MD, Davies D, Mackillop WJ. Prognostic factors in non-small cell lung cancer: a decade of progress. Chest 2002;122:1037-57. https://doi.org/10.1378/chest.122.3.1037
  2. Groome PA, Bolejack V, Crowley JJ, Kennedy C, Krasnik M, Sobin LH, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007;2:694-705. https://doi.org/10.1097/JTO.0b013e31812d05d5
  3. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell 1994;79:13-21. https://doi.org/10.1016/0092-8674(94)90396-4
  4. Hoeller D, Dikic I. Targeting the ubiquitin system in cancer therapy. Nature 2009;458:438-44. https://doi.org/10.1038/nature07960
  5. Su V, Lau AF. Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation. Cell Mol Life Sci 2009;66:2819-33. https://doi.org/10.1007/s00018-009-0048-9
  6. White RE, Powell DJ, Berry C. HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites. FASEB J 2011;25:1729-36. https://doi.org/10.1096/fj.10-178947
  7. Gills JJ, Lopiccolo J, Tsurutani J, Shoemaker RH, Best CJ, Abu-Asab MS, et al. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res 2007; 13:5183-94. https://doi.org/10.1158/1078-0432.CCR-07-0161
  8. Gills JJ, Lopiccolo J, Dennis PA. Nelfinavir, a new anti- cancer drug with pleiotropic effects and many paths to autophagy. Autophagy 2008;4:107-9. https://doi.org/10.4161/auto.5224
  9. Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I nonsmall cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003. Cancer 2007;110:1532-41. https://doi.org/10.1002/cncr.22938
  10. Chansky K, Sculier JP, Crowley JJ, Giroux D, Van Meerbeeck J, Goldstraw P, et al. The International Association for the Study of Lung Cancer Staging Project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol 2009;4:792-801. https://doi.org/10.1097/JTO.0b013e3181a7716e
  11. Kaplun L, Tzirkin R, Bakhrat A, Shabek N, Ivantsiv Y, Raveh D. The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated degradation of Ho endonuclease. Mol Cell Biol 2005;25:5355-62. https://doi.org/10.1128/MCB.25.13.5355-5362.2005
  12. Wilkinson CR, Wallace M, Morphew M, Perry P, Allshire R, Javerzat JP, et al. Localization of the 26S proteasome during mitosis and meiosis in fission yeast. EMBO J 1998;17:6465-76. https://doi.org/10.1093/emboj/17.22.6465
  13. Kumatori A, Tanaka K, Inamura N, Sone S, Ogura T, Matsumoto T, et al. Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci USA 1990;87:7071-5. https://doi.org/10.1073/pnas.87.18.7071
  14. Kanayama H, Tanaka K, Aki M, Kagawa S, Miyaji H, Satoh M, et al. Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells. Cancer Res 1991;51:6677-85.
  15. Goldknopf IL, Wilson G, Ballal NR, Busch H. Chromatin conjugate protein A24 is cleaved and ubiquitin is lost during chicken erythropoiesis. J Biol Chem 1980;255: 10555-8.
  16. Agell N, Mezquita C. Cellular content of ubiquitin and formation of ubiquitin conjugates during chicken spermatogenesis. Biochem J 1988;250:883-9. https://doi.org/10.1042/bj2500883
  17. Ishibashi Y, Takada K, Joh K, Ohkawa K, Aoki T, Matsuda M. Ubiquitin immunoreactivity in human malignant tumours. Br J Cancer 1991;63:320-2. https://doi.org/10.1038/bjc.1991.75