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Article

Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma

  • Authors:
    • Ling Peng
    • Zesong Yang
    • Cui Tan
    • Guosheng Ren
    • Jianbin Chen
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
  • Pages: 1055-1061
    |
    Published online on: January 28, 2013
       https://doi.org/10.3892/mmr.2013.1291
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Abstract

A disintegrin‑like and metalloprotease with thrombospondin type Ⅰ motifs (ADAMTS) are a family of 19 secreted mammalian metalloproteases. ADAMTS9 was reported to be a novel tumor suppressor gene and is downregulated in various types of human cancer due to hypermethylation of promoter CpG islands. In the present study, the silencing mechanism of the ADAMTS9 gene was analyzed in the multiple myeloma (MM) cell lines, KM3 and RPMI‑8226. Control and MM samples were obtained by conventional bone marrow (BM) biopsy of normal and MM adult BM, respectively. RT‑PCR revealed a high expression of the ADAMTS9 gene in normal samples and RPMI‑8226 cells while marked gene silencing of ADAMTS9 was observed in MM patients and KM3 cells. Promoter methylation of ADAMTS9 was detected in the KM3 cell line and 66% (37/56) MM patients by methylation‑specific PCR. In addition, the DNA demethylating agent, 5‑aza‑2'‑deoxycytidine and trichostatin A restored ADAMTS9 expression by suppressing promoter methylation in KM3 cells. Ectopic expression of ADAMTS9 in ADAMTS9‑silenced MM cells was found to significantly suppress cell colony formation and proliferation. In the present study, DNA methylation was found to play a key role in ADAMTS9 gene silencing and the biological behavior of myeloma cells. The results demonstrate that ADAMTS9 silencing by methylation may be a novel tumor marker for MM and the applicability of demethylating agents in the treatment of MM.
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1 

Hatzimichael E, Dasoula A, Benetatos L, et al: Study of specific genetic and epigenetic variables in multiple myeloma. Leuk Lymphoma. 51:2270–2274. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Rajumar SV and Greipp PR: Prognostic factors in multiple myeloma. Hematol Oncol Clin North Am. 13:1295–1314. 1999. View Article : Google Scholar

3 

Kyle RA and Rajkumar SV: Multiple myeloma. N Engl J Med. 351:1860–1873. 2004. View Article : Google Scholar

4 

Klein U, Jauch A, Hielscher T, et al: Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. 117:2136–2144. 2011.

5 

Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar

6 

Jost E, Gezer D, Wilop S, et al: Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma. Cancer Lett. 281:24–31. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Boultwood J and Wainscoat JS: Gene silencing by DNA methylation in haematological malignancies. Br J Haematol. 138:3–11. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Yuregir OO, Yurtcu E, Kizilkilic E, Kocer NE, Ozdogu H and Sahin FI: Detecting methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patients. Int J Lab Hematol. 32:142–149. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Braggio E, Maiolino A, Gouveia ME, et al: Methylation status of nine tumor suppressor genes in multiple myeloma. Int J Hematol. 91:87–96. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Ullmannova-Benson V, Guan M, Zhou X, et al: DLC1 tumor suppressor gene inhibits migration and invasion of multiple myeloma cells through RhoA GTPase pathway. Leukemia. 23:383–390. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Galm O, Yoshikawa H, Esteller M, Osieka R and Herman JG: SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood. 101:2784–2788. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Levy GG, Nichols WC, Lian EC, et al: Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 413:488–494. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Lo PH, Lung H, Cheung AK, et al: Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis. Cancer Res. 70:5567–5576. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Lung HL, Lo PH, Xie D, et al: Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9 and its association with lymph node metastases in nasopharyngeal carcinoma. Int J Cancer. 123:401–408. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Zhang C, Shao Y, Zhang W, et al: High-resolution melting analysis of ADAMTS9 methylation levels in gastric, colorectal and pancreatic cancers. Cancer Gene Cytogenet. 196:38–44. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Kuo HK, Griffith JD and Kreuzer KN: 5-Azacytidine induced methyltransferase-DNA adducts block DNA replication in vivo. Cancer Res. 17:8248–8254. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Sidransky D: Emerging molecular markers of cancer. Nat Rev Cancer. 2:210–219. 2002. View Article : Google Scholar

18 

de Carvalho F, Colleoni GW, Almeida MS, Carvalho AL and Vettore AL: TGFβR2 aberrant methylation is a potential prognostic marker and therapeutic target in multiple myeloma. Int J Cancer. 125:1985–1991. 2009.

19 

Lo PH, Leung AC, Kwok CY, et al: Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene. 26:148–157. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Li Z, Zhang W, Shao Y, et al: High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers. Med Oncol. 27:998–1004. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Moncada-Pazos A, Obaya AJ, Fraga MF, et al: The ADAMTS12 metalloprotease gene is epigenetically silenced in tumor cells and transcriptionally activated in the stroma during progression of colon cancer. J Cell Sci. 122:2906–2913. 2009. View Article : Google Scholar

22 

Viloria CG, Obaya AJ, Moncada-Pazos A, et al: Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer. Cancer Res. 69:4926–4934. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Dunn JR, Panutsopulo D, Shaw MW, et al: METH-2 silencing and promoter hypermethylation in NSCLC. Br J Cancer. 91:1149–1154. 2004.PubMed/NCBI

24 

Dubail J, Kesteloot F, Deroanne C, et al: ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity. Cell Mol Life Sci. 67:4213–4232. 2010. View Article : Google Scholar : PubMed/NCBI

25 

EI Hour M, Moncada-Pazos A, Blacher S, et al: Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis. Oncogene. 29:3025–3032. 2010.PubMed/NCBI

26 

Dunn JR, Reed JE, du Plessis DG, et al: Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours. Br J Cancer. 94:1186–1193. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Koo BH, Coe DM, Dixon LJ, et al: ADAMTS9 is a cell-autonomously acting, anti-angiogenic metalloprotease expressed by microvascular endothelial cells. Am J Pathol. 176:1494–1504. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Peng L, Yang Z, Tan C, Ren G and Chen J: Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma. Mol Med Rep 7: 1055-1061, 2013.
APA
Peng, L., Yang, Z., Tan, C., Ren, G., & Chen, J. (2013). Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma. Molecular Medicine Reports, 7, 1055-1061. https://doi.org/10.3892/mmr.2013.1291
MLA
Peng, L., Yang, Z., Tan, C., Ren, G., Chen, J."Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma". Molecular Medicine Reports 7.3 (2013): 1055-1061.
Chicago
Peng, L., Yang, Z., Tan, C., Ren, G., Chen, J."Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma". Molecular Medicine Reports 7, no. 3 (2013): 1055-1061. https://doi.org/10.3892/mmr.2013.1291
Copy and paste a formatted citation
x
Spandidos Publications style
Peng L, Yang Z, Tan C, Ren G and Chen J: Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma. Mol Med Rep 7: 1055-1061, 2013.
APA
Peng, L., Yang, Z., Tan, C., Ren, G., & Chen, J. (2013). Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma. Molecular Medicine Reports, 7, 1055-1061. https://doi.org/10.3892/mmr.2013.1291
MLA
Peng, L., Yang, Z., Tan, C., Ren, G., Chen, J."Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma". Molecular Medicine Reports 7.3 (2013): 1055-1061.
Chicago
Peng, L., Yang, Z., Tan, C., Ren, G., Chen, J."Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma". Molecular Medicine Reports 7, no. 3 (2013): 1055-1061. https://doi.org/10.3892/mmr.2013.1291
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