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ADRM1 gene amplification is a candidate driver for metastatic gastric cancers

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Abstract

We searched for candidate target genes in metastatic gastric cancer, using comparative genomic hybridization (CGH) and mRNA expression array analysis of endoscopic biopsy samples collected from 32 patients. Recurrent amplicons included 17q21.2 (36,569,293–37,307,055), 8q24.13-q24.21 (126,357,475–130,159,285), and 20q13.33 (60,211,249–61,382,787). In this paper, we focused on the 1.1-Mb genomic region containing 24 genes in chromosome 20q13.33 (from 60,211,249 to 61,382,787), the third most frequent amplicon that was amplified in three of 32 patients (9.4 %), with log2 tumor/reference ratios ranging from 0.6 to 1.5. Of three genes in the 20q13.33 amplicon, ADRM1 was chosen for functional analyses. ADRM1 knockdown suppressed the proliferation of two human gastric cancer cells, SNU-601 and SNU-216. Overexpression of Adrm1 promoted cell proliferation of conditionally-immortalized, mouse ImSt gastric epithelial cells, with increased S1 phase fraction and decreased expression of p21(Cip1). These results collectively indicate that ADRM1 promoted gastric epithelial cell proliferation by cell cycle progression. Therefore, ADRM1 is a candidate target gene in the chromosome 20q13.33 amplicon that may possibly be linked to development of gastric cancer.

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Abbreviations

CGH:

Comparative genomic hybridization

EGFP:

Enhanced green fluorescent protein

ANOVA:

Analysis of variance

FISH:

Fluorescence in situ hybridization

FFPE:

Formalin-fixed: paraffin-embedded

FITC:

Fluorescein isothiocyanate

FACS:

Fluorescence-activated cell sorting

TMA:

Tissue microarray

References

  1. Alberts S, Cervantes A, van de Velde C (2003) Gastric cancer: epidemiology, pathology, and treatment. Ann Oncol 14(Suppl 2):ii31–ii36

    PubMed  Google Scholar 

  2. Kim HK, Green JE (2014) Predictive biomarker candidates for the response of gastric cancer to targeted and cytotoxic agents. Pharmacogenomics 15(3):375–384

    Article  CAS  PubMed  Google Scholar 

  3. Kim HK, Choi IJ, Kim CG, Kim HS, Oshima A, Yamada Y, Arao T, Nishio K, Michalowski A, Green JE (2012) Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy. Pharmacogenomics J 12(2):119–127

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Kim HK, Choi IJ, Kim CG, Kim HS, Oshima A, Michalowski A, Green JE (2011) A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients. PLoS ONE 6(2):e16694

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Cheng L, Wang P, Yang S, Yang Y, Zhang Q, Zhang W, Xiao H, Gao H, Zhang Q (2012) Identification of genes with a correlation between copy number and expression in gastric cancer. BMC Med Genomics 5:14

    Article  PubMed Central  PubMed  Google Scholar 

  6. Fan B, Dachrut S, Coral H, Yuen ST, Chu KM, Law S, Zhang L, Ji J, Leung SY, Chen X (2012) Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer. PLoS ONE 7(4):e29824

  7. Tabach Y, Kogan-Sakin I, Buganim Y, Solomon H, Goldfinger N, Hovland R, Ke XS, Oyan AM, Kalland KH, Rotter V, Domany E (2011) Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer. PLoS ONE 6(1):e14632

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I (2008) Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453(7194):481–488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Fejzo MS, Dering J, Ginther C, Anderson L, Ramos L, Walsh C, Karlan B, Slamon DJ (2008) Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as amplification target. Genes Chromosomes Cancer 47(10):873–883

    Article  CAS  PubMed  Google Scholar 

  10. Chen W, Hu XT, Shi QL, Zhang FB, He C (2009) Knockdown of the novel proteasome subunit Adrm1 located on the 20q13 amplicon inhibits colorectal cancer cell migration, survival and tumorigenicity. Oncol Rep 21(2):531–537

    CAS  PubMed  Google Scholar 

  11. Yan F, Cao H, Chaturvedi R, Krishna U, Hobbs SS, Dempsey PJ, Peek RM Jr, Cover TL, Washington MK, Wilson KT, Polk DB (2009) Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis. Gastroenterology 136(4):1297–1307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Schreiner P, Chen X, Husnjak K, Randles L, Zhang N, Elsasser S, Finley D, Dikic I, Walters KJ, Groll M (2008) Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction. Nature 453(7194):548–552

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A (2003) UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Cancer Res 63(14):4167–4173

    CAS  PubMed  Google Scholar 

  14. Yao T, Song L, Xu W, DeMartino GN, Florens L, Swanson SK, Washburn MP, Conaway RC, Conaway JW, Cohen RE (2006) Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol 8(9):994–1002

    CAS  PubMed  Google Scholar 

  15. Hamazaki J, Iemura S, Natsume T, Yashiroda H, Tanaka K, Murata S (2006) A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes. EMBO J 25(19):4524–4536

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Qiu XB, Ouyang SY, Li CJ, Miao S, Wang L, Goldberg AL (2006) hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37. EMBO J 25(24):5742–5753

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Tsafrir D, Bacolod M, Selvanayagam Z, Tsafrir I, Shia J, Zeng Z, Liu H, Krier C, Stengel RF, Barany F, Gerald WL, Paty PB, Domany E, Notterman DA (2006) Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res 66:2129–2137

    Article  CAS  PubMed  Google Scholar 

  18. Hodgson JG, Chin K, Collins C, Gray JW (2003) Genome amplification of chromosome 20 in breast cancer. Breast Cancer Res Treat 78:337–345

    Article  CAS  PubMed  Google Scholar 

  19. Alers JC, Krijtenburg PJ, Vis AN, Hoedemaeker RF, Wildhagen MF, Hop WC, van Der Kwast TT, Schröder FH, Tanke HJ, van Dekken H (2001) Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies: early cancers may contain aggressive genetic features. Am J Pathol 158:399–406

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Mahlamaki EH, Barlund M, Tanner M, Gorunova L, Hoglund M, Karhu R, Kallioniemi A (2002) Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chromosomes Cancer 35:353–358

    Article  CAS  PubMed  Google Scholar 

  21. Anchoori RK, Karanam B, Peng S, Wang JW, Jiang R, Tanno T, Orlowski RZ, Matsui W, Zhao M, Rudek MA, Hung CF, Chen X, Walters KJ, Roden RB (2013) A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell 24(6):791–805

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Proteogenomic Research Program and 2013K000429 funded by the Korean Ministry of Science, ICT, and Future Planning and by National Cancer Center Grant 1210051 and 1410850.

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Authors have nothing to disclose.

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Authors and Affiliations

  1. Biomolecular Function Research Branch, National Cancer Center, 323 Ilsanro, Ilsandong, Goyang, 410-769, Gyeonggi, Republic of Korea

    Seok Hoon Jang, Jun Won Park, Hyo Rim Kim & Hark Kyun Kim

  2. Seoul National University, Seoul, 151-742, Republic of Korea

    Seok Hoon Jang & Je Kyung Seong

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  1. Seok Hoon Jang
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  2. Jun Won Park
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  3. Hyo Rim Kim
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  4. Je Kyung Seong
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Correspondence to Hark Kyun Kim.

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Jang, S.H., Park, J.W., Kim, H.R. et al. ADRM1 gene amplification is a candidate driver for metastatic gastric cancers. Clin Exp Metastasis 31, 727–733 (2014). https://doi.org/10.1007/s10585-014-9663-4

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  • DOI: https://doi.org/10.1007/s10585-014-9663-4

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