Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

详细信息    查看全文

• 作者：Gangshi Wang (9)
  Jie Gao (10)
  Haili Huang (9)
  Yu Tian (9)
  Liyan Xue (12)
  Weihua Wang (9)
  Weidi You (9)
  Hongwei Lian (9)
  Xiaojian Duan (9)
  Benyan Wu (9)
  Mengwei Wang (11)
  
• 关键词：Gastric carcinoma ; Long interspersed nuclear element ; 1 endonuclease ; GCRG213 protein ; Tissue microarray
• 刊名：BMC Cancer
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：558KB
• 参考文献：1. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W: Initial sequencing and analysis of the human genome. / Nature 2001,409(6822):860-21. CrossRef
  2. Brouha B, Schustak J, Badge RM, Lutz-Prigge S, Farley AH, Moran JV, Kazazian HH Jr: Hot L1s account for the bulk of retrotransposition in the human population. / Proc Natl Acad Sci USA 2003,100(9):5280-285. CrossRef
  3. Scott AF, Schmeckpeper BJ, Abdelrazik M, Comey CT, O'Hara B, Rossiter JP, Cooley T, Heath P, Smith KD, Margolet L: Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence. / Genomics 1987,1(2):113-25. CrossRef
  4. Basame S, Wai-lun Li P, Howard G, Branciforte D, Keller D, Martin SL: Spatial assembly and RNA binding stoichiometry of a LINE-1 protein essential for retrotransposition. / J Mol Biol 2006,357(2):351-57. CrossRef
  5. Martin SL, Bushman D, Wang F, Li PW, Walker A, Cummiskey J, Branciforte D, Williams MC: A single amino acid substitution in ORF1 dramatically decreases L1 retrotransposition and provides insight into nucleic acid chaperone activity. / Nucleic Acids Res 2008,36(18):5845-854. CrossRef
  6. Feng Q, Moran JV, Kazazian HH Jr, Boeke JD: Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. / Cell 1996,87(5):905-16. CrossRef
  7. Mathias SL, Scott AF, Kazazian HH Jr, Boeke JD, Gabriel A: Reverse transcriptase encoded by a human transposable element. / Science 1991,254(5039):1808-810. CrossRef
  8. Jurka J: Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons. / Proc Natl Acad Sci USA 1997,94(5):1872-877. CrossRef
  9. Soifer HS, Zaragoza A, Peyvan M, Behlke MA, Rossi JJ: A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon. / Nucleic Acids Res 2005,33(3):846-56. CrossRef
  10. Garcia-Perez JL, Morell M, Scheys JO, Kulpa DA, Morell S, Carter CC, Hammer GD, Collins KL, O'Shea KS, Menendez P: Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells. / Nature 2010,466(7307):769-73. CrossRef
  11. St Laurent G 3rd, Hammel N, McCaffrey TA: A LINE-1 component to human aging: do LINE elements exact a longevity cost for evolutionary advantage? / Mech Ageing Dev 2010,131(5):299-05. CrossRef
  12. Harris CR, Normart R, Yang Q, Stevenson E, Haffty BG, Ganesan S, Cordon-Cardo C, Levine AJ, Tang LH: Association of nuclear localization of a long interspersed nuclear element-1 protein in breast tumors with poor prognostic outcomes. / Genes Cancer 2010,1(2):115-24. CrossRef
  13. Su Y, Davies S, Davis M, Lu H, Giller R, Krailo M, Cai Q, Robison L, Shu XO: Expression of LINE-1 p40 protein in pediatric malignant germ cell tumors and its association with clinicopathological parameters: a report from the Children's Oncology Group. / Cancer Lett 2007,247(2):204-12. CrossRef
  14. Ting DT, Lipson D, Paul S, Brannigan BW, Akhavanfard S, Coffman EJ, Contino G, Deshpande V, Iafrate AJ, Letovsky S: Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. / Science 2011,331(6017):593-96. CrossRef
  15. Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG: CpG island methylation in premalignant stages of gastric carcinoma. / Cancer Res 2001,61(7):2847-851.
  16. Wilhelm CS, Kelsey KT, Butler R, Plaza S, Gagne L, Zens MS, Andrew AS, Morris S, Nelson HH, Schned AR: Implications of LINE1 methylation for bladder cancer risk in women. / Clin Cancer Res 2010,16(5):1682-689. CrossRef
  17. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, Giovannucci EL, Fuchs CS: A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. / J Natl Cancer Inst 2008,100(23):1734-738. CrossRef
  18. Tangkijvanich PHN, Rattanatanyong P, Wisedopas N, Mahachai V, Mutirangura A: Serum LINE-1 hypomethylation as a potential prognostic marker for hepatocellular carcinoma. / Clin Chim Acta 2007,379(1-):127-33. CrossRef
  19. Wallace NA, Belancio VP, Deininger PL: L1 mobile element expression causes multiple types of toxicity. / Gene 2008,419(1-):75-1. CrossRef
  20. Belancio VP, Roy-Engel AM, Pochampally RR, Deininger P: Somatic expression of LINE-1 elements in human tissues. / Nucleic Acids Res 2010,38(12):3909-922. CrossRef
  21. Kuo KWSH, Huang YS, Leung WC: Expression of transposon LINE-1 is relatively human-specific and function of the transcripts may be proliferation-essential. / Biochem Biophys Res Commun 1998,253(3):566-70. CrossRef
  22. Wang GS, Wang MW, Wu BY, Liu XB, You WD, Yang XY: A gene encoding an apurinic/apyrimidinic endonuclease-like protein is up-regulated in human gastric cancer. / World J Gastroenterol 2003,9(6):1196-201.
  23. Wang G, Huang H, Gao J, Chen P, You W, Wu B, Wang M: Tissue microarray analysis of topoisomerase IIalpha protein in gastric adenocarcinomas: histogenetic and prognostic implications. / Cancer Genomics Proteomics 2003,8(3):127-33.
  24. Wu YQ, Wu BY, Wang GS, You WD, Wang WH, Wang MW: Preparation and identification of monoclonal antibody against human GCRG213. / Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2012,28(1):46-8.
  25. Going JJ, Stuart RC, Downie M, Fletcher-Monaghan AJ, Keith WN: 'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract. / J Pathol 2002,196(4):394-00. CrossRef
  26. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. / Proc Natl Acad Sci USA 1996,93(18):9821-826. CrossRef
  27. Iacopetta B, Grieu F, Phillips M, Ruszkiewicz A, Moore J, Minamoto T, Kawakami K: Methylation levels of LINE-1 repeats and CpG island loci are inversely related in normal colonic mucosa. / Cancer Sci 2007,98(9):1454-460. CrossRef
  28. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. / Nucleic Acids Res 1997,25(17):3389-402. CrossRef
  29. Zingler N, Weichenrieder O, Schumann GG: APE-type non-LTR retrotransposons: determinants involved in target site recognition. / Cytogenet Genome Res 2005,110(1-):250-68. CrossRef
  30. Weichenrieder O, Repanas K, Perrakis A: Crystal structure of the targeting endonuclease of the human LINE-1 retrotransposon. / Structure 2004,12(6):975-86. CrossRef
  31. Sciamanna I, Landriscina M, Pittoggi C, Quirino M, Mearelli C, Beraldi R, Mattei E, Serafino A, Cassano A, Sinibaldi-Vallebona P: Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. / Oncogene 2005,24(24):3923-931. CrossRef
  32. Carlini FRB, Molinari A, Parisi C, Bozzuto G, Toccacieli L, Formisano G, De Orsi D, Paradisi S, Grober OM, Ravo M, Weisz A, Arcieri R, Vella S, Gaudi S: The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines. / PLoS One 2010,5(12):e14221. CrossRef
  33. Banaz-Yasar F, Steffen G, Hauschild J, Bongartz BM, Schumann GG, Ergun S: LINE-1 retrotransposition events affect endothelial proliferation and migration. / Histochem Cell Biol 2010,134(6):581-89. CrossRef
  34. Oricchio E, Sciamanna I, Beraldi R, Tolstonog GV, Schumann GG, Spadafora C: Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression. / Oncogene 2007,26(29):4226-233. CrossRef
  35. Bae JM, Shin SH, Kwon HJ, Park SY, Kook MC, Kim YW, Cho NY, Kim N, Kim TY, Kim D, Kang GH: ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. / Int J Cancer 2012,131(6):1323-331. CrossRef
  36. Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H: LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis. / Gastric Cancer 2012. doi:10.1007/s10120-012-0209-7.
  37. Leung WK, Ng EK, Chan WY, Auyeung AC, Chan KF, Lam CC, Chan FK, Lau JY, Sung JJ: Risk factors associated with the development of intestinal metaplasia in first-degree relatives of gastric cancer patients. / Cancer Epidemiol Biomarkers Prev 2005,14(12):2982-986. CrossRef
  38. Bollati VSJ, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P, Baccarelli A: Decline in genomic DNA methylation through aging in a cohort of elderly subjects. / Mech Ageing Dev 2009,130(4):234-39. CrossRef
  39. Jintaridth P, Mutirangura A: Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. / Physiol Genomics 2010,41(2):194-00. CrossRef
  40. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/265/prepub
  
• 作者单位：Gangshi Wang (9)
  Jie Gao (10)
  Haili Huang (9)
  Yu Tian (9)
  Liyan Xue (12)
  Weihua Wang (9)
  Weidi You (9)
  Hongwei Lian (9)
  Xiaojian Duan (9)
  Benyan Wu (9)
  Mengwei Wang (11)
  
  9. Department of Geriatric Gastroenterology, China PLA General Hospital, Beijing, China
  10. Department of Pathology, China PLA General Hospital, Beijing, China
  12. Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  11. Department of Geriatric Medicine, China PLA General Hospital, Beijing, China
  
• ISSN：1471-2407

文摘

Background Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. Methods Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. Results Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (?5 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN. Conclusions GCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor.