Biopolym. Cell. 2015; 31(6):458-464.
Molecular Biomedicine
Aberrant expression of metallothioneins in clear cell renal cell carcinomas
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - National Cancer Institute
33/43, Lomonosova Str., Kyiv, Ukraine, 03022
Abstract
Aim. To find candidate tumor suppressor genes among metallothioneins for clear cell renal cell carcinoma. Methods. Analysis of the microarray data, quantitative PCR. Results. We found three genes encoding metallothioneines that showed reduced expression in different types of renal tumors, using protocol of the cross-platform meta-analysis of microarray data with normalization on several reference genes. Decreased expression of the MT1G, MT1F, and MT1H genes in clear cell renal cell carcinoma was confirmed by qPCR. Conclusions. The MT1G, MT1F and MT1H genes as well as may be considered as the candidate tumor suppressor genes for ccRCC.
Keywords: metallothionein, renal tumors, candidate tumor suppressor gene, microarrays
Full text: (PDF, in English)
References
[1]
Tai SK, Tan OJ, Chow VT, Jin R, Jones JL, Tan PH, Jayasurya A, Bay BH. Differential expression of metallothionein 1 and 2 isoforms in breast cancer lines with different invasive potential: identification of a novel nonsilent metallothionein-1H mutant variant. Am J Pathol. 2003;163(5):2009-19.
[2]
Vandeghinste N, Proost P, De Ley M. Metallothionein isoform gene expression in zinc-treated human peripheral blood lymphocytes. Cell Mol Biol (Noisy-le-grand). 2000;46(2):419-33.
[3]
Ferrario C, Lavagni P, Gariboldi M, Miranda C, Losa M, Cleris L, Formelli F, Pilotti S, Pierotti MA, Greco A. Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma. Lab Invest. 2008;88(5):474-81.
[4]
Han YC, Zheng ZL, Zuo ZH, Yu YP, Chen R, Tseng GC, Nelson JB, Luo JH. Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1. J Pathol. 2013;230(2):184-93.
[5]
Sakamoto LH, DE Camargo B, Cajaiba M, Soares FA, Vettore AL. MT1G hypermethylation: a potential prognostic marker for hepatoblastoma. Pediatr Res. 2010;67(4):387-93.
[6]
Roth MJ, Abnet CC, Hu N, Wang QH, Wei WQ, Green L, D'Alelio M, Qiao YL, Dawsey SM, Taylor PR, Woodson K. p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions. Oncol Rep. 2006;15(6):1591-7.
[7]
Morris MR, Hesson LB, Wagner KJ, Morgan NV, Astuti D, Lees RD, Cooper WN, Lee J, Gentle D, Macdonald F, Kishida T, Grundy R, Yao M, Latif F, Maher ER. Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma. Oncogene. 2003;22(43):6794-801.
[8]
Yan DW, Fan JW, Yu ZH, Li MX, Wen YG, Li DW, Zhou CZ, Wang XL, Wang Q, Tang HM, Peng ZH. Downregulation of metallothionein 1F, a putative oncosuppressor, by loss of heterozygosity in colon cancer tissue. Biochim Biophys Acta. 2012;1822(6):918-26.
[9]
Nagai H, Ponglikitmongkol M, Fujimoto J, Yamamoto H, Kim YS, Konishi N, Matsubara K. Genomic aberrations in early stage human hepatocellular carcinomas. Cancer. 1998;82(3):454-61.
[10]
Nguyen A, Jing Z, Mahoney PS, Davis R, Sikka SC, Agrawal KC, Abdel-Mageed AB. In vivo gene expression profile analysis of metallothionein in renal cell carcinoma. Cancer Lett. 2000;160(2):133-40.
[11]
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034.
[12]
Spiess AN, Feig C, Ritz C. Highly accurate sigmoidal fitting of real-time PCR data by introducing a parameter for asymmetry. BMC Bioinformatics. 2008;9:221.
[13]
Kanda M, Nomoto S, Okamura Y, Nishikawa Y, Sugimoto H, Kanazumi N, Takeda S, Nakao A. Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis. Int J Oncol. 2009;35(3):477-83.
[14]
Morris MR, Gentle D, Abdulrahman M, Clarke N, Brown M, Kishida T, Yao M, Teh BT, Latif F, Maher ER. Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Br J Cancer. 2008;98(2):496-501.
[15]
Arriaga JM, Levy EM, Bravo AI, Bayo SM, Amat M, Aris M, Hannois A, Bruno L, Roberti MP, Loria FS, Pairola A, Huertas E, Mordoh J, Bianchini M. Metallothionein expression in colorectal cancer: relevance of different isoforms for tumor progression and patient survival. Hum Pathol. 2012;43(2):197-208.
[16]
Henrique R, JerГіnimo C, Hoque MO, Nomoto S, Carvalho AL, Costa VL, Oliveira J, Teixeira MR, Lopes C, Sidransky D. MT1G hypermethylation is associated with higher tumor stage in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(5):1274-8.
[17]
Lu DD, Chen YC, Zhang XR, Cao XR, Jiang HY, Yao L. The relationship between metallothionein-1F (MT1F) gene and hepatocellular carcinoma. Yale J Biol Med. 2003;76(2):55-62.