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Medical Oncology

, 30:715 | Cite as

Up-regulation of tripartite motif-containing 29 promotes cancer cell proliferation and predicts poor survival in colorectal cancer

  • Tao Jiang
  • Hua-mei Tang
  • Su Lu
  • Dong-wang Yan
  • Yin-xue Yang
  • Zhi-hai Peng
Original Paper

Abstract

Tripartite motif-containing 29 (TRIM29), also known as ataxia-telangiectasia group D, is structurally a member of the tripartite motif family of proteins, which characterized by the conserved RING finger, B-box, and coiled-coil domains. TRIM29 functions as an oncogene or a tumor suppressor depending on the tumor types. In this study, we aim to evaluate whether TRIM29 affects the tumorigenesis and progression of colorectal cancer. The expression of TRIM29 was investigated using real-time PCR in 40 pairs of colorectal cancer tissues and immunohistochemistry on a tissue microarray containing 203 cases of primary colorectal cancer paired with non-cancerous tissues. Down-regulation of TRIM29 was achieved by transient transfection in RKO cell lines, and the effects of TRIM29 on tumor proliferation were evaluated by MTT and plate colony formation assays. Results indicated that TRIM29 expression was much higher in colorectal cancer tissues and significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, ki-67 index, and advanced tumor stage. Patients with TRIM29-positive tumors had a higher recurrence rate and poorer survival than patients with TRIM29-negative tumors. In multivariate analyses, the TRIM29 expression was an independent factor for determining colorectal cancer prognosis after surgery. Moreover, down-regulation of TRIM29 inhibited tumor cell proliferation in vitro. In conclusion, TRIM29 plays an important role in promoting colorectal cancer progression. Our findings suggest that TRIM29 may serve as a novel biomarker for tumor recurrence and survival for colorectal cancer patients.

Keywords

Tripartite motif-containing 29 Colorectal cancer Prognosis Immunohistochemistry 

Notes

Acknowledgments

The project was supported by the grants from National Natural Science Foundation of China (81072008, 81172328) and Medical engineering crossing project grant funded by Shanghai Jiaotong University (YG2011MS59).

Conflicts of interest

None.

References

  1. 1.
    Jemal A, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.CrossRefPubMedGoogle Scholar
  2. 2.
    Gaedcke J, et al. The rectal cancer microRNAome–microRNA expression in rectal cancer and matched normal mucosa. Clin Cancer Res. 2012;18(18):4919–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Siegel R, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.CrossRefPubMedGoogle Scholar
  4. 4.
    Zhang S, et al. Changes on the disease pattern of primary colorectal cancers in Southern China: a retrospective study of 20 years. Int J Colorectal Dis. 2009;24(8):943–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Schepeler T, et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 2008;68(15):6416–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Compton CC, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124(7):979–94.PubMedGoogle Scholar
  7. 7.
    Nakamura Y, et al. Case of the multiple liver metastases from colon cancer obtained long-term disease-free survival with multimodality therapy. Gan To Kagaku Ryoho. 2012;39(12):2228–30.PubMedGoogle Scholar
  8. 8.
    Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479–507.CrossRefPubMedGoogle Scholar
  9. 9.
    Yamaguchi H, Hsu JL, Hung MC. Regulation of ubiquitination-mediated protein degradation by survival kinases in cancer. Front Oncol. 2012;2:15.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Reymond A, et al. The tripartite motif family identifies cell compartments. EMBO J. 2001;20(9):2140–51.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Quaderi NA, et al. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet. 1997;17(3):285–91.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang L, et al. Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization. Cancer Cell. 2009;15(3):207–19.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Kosaka Y, et al. Tripartite motif-containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer. Ann Surg Oncol. 2007;14(9):2543–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Mutter GL, et al. Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation. Gynecol Oncol. 2001;83(2):177–85.CrossRefPubMedGoogle Scholar
  15. 15.
    Santin AD, et al. Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer. 2004;112(1):14–25.CrossRefPubMedGoogle Scholar
  16. 16.
    Dyrskjot L, et al. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res. 2004;64(11):4040–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Hawthorn L, et al. Characterization of cell-type specific profiles in tissues and isolated cells from squamous cell carcinomas of the lung. Lung Cancer. 2006;53(2):129–42.CrossRefPubMedGoogle Scholar
  18. 18.
    Li D, et al. IMP3 is a novel prognostic marker that correlates with colon cancer progression and pathogenesis. Ann Surg Oncol. 2009;16(12):3499–506.CrossRefPubMedGoogle Scholar
  19. 19.
    Wang X, et al. Reduced expression of PER3 is associated with incidence and development of colon cancer. Ann Surg Oncol. 2012;19(9):3081–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Yan DW, et al. Ubiquitin D is correlated with colon cancer progression and predicts recurrence for stage II-III disease after curative surgery. Br J Cancer. 2010;103(7):961–9.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Reddy BA, Etkin LD, Freemont PS. A novel zinc finger coiled-coil domain in a family of nuclear proteins. Trends Biochem Sci. 1992;17(9):344–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Borden KL. RING fingers and B-boxes: zinc-binding protein–protein interaction domains. Biochem Cell Biol. 1998;76(2–3):351–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Leonhardt EA, et al. Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC). Genomics. 1994;19(1):130–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Sardiello M, et al. Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties. BMC Evol Biol. 2008;8:225.CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Brzoska PM, et al. The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. Proc Natl Acad Sci U S A. 1995;92(17):7824–8.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Lawson JC, Blatch GL, Edkins AL. Cancer stem cells in breast cancer and metastasis. Breast Cancer Res Treat. 2009;118(2):241–54.CrossRefPubMedGoogle Scholar
  27. 27.
    Yuan Z, et al. The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions. Mol Cell Biol. 2010;30(12):3004–15.CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Sho T, et al. TRIM29 negatively regulates p53 via inhibition of Tip60. Biochim Biophys Acta. 2011;1813(6):1245–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Shibata MA, et al. Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. Cancer Gene Ther. 2001;8(1):23–35.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of General SurgeryShanghai Jiao Tong University Affiliated First People’s HospitalShanghaiPeople’s Republic of China
  2. 2.Department of PathologyShanghai Jiao Tong University Affiliated First People’s HospitalShanghaiPeople’s Republic of China
  3. 3.Department of Anal-Colorectal SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanPeople’s Republic of China

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