• 中國醫(yī)科大學(xué)附屬第一醫(yī)院腫瘤外科（沈陽110001）;

目的 　探討組蛋白修飾與胃腸道惡性腫瘤的關(guān)系。
方法 　復(fù)習(xí)組蛋白修飾以及組蛋白修飾與胃腸道惡性腫瘤之間關(guān)系的相關(guān)文獻并進行綜述。
結(jié)果 　組蛋白的修飾為表遺傳改變之一，能導(dǎo)致基因表達的改變，在惡性腫瘤的發(fā)生、發(fā)展中起重要作用。DNA甲基化與組蛋白修飾間相互作用，形成復(fù)雜系統(tǒng)，維持基因沉默。表觀遺傳修飾具有可逆性，逆轉(zhuǎn)表觀遺傳修飾，從而改變基因表達狀態(tài)，可能使惡性腫瘤細胞正常化（稱為表觀基因治療）。表觀基因治療對于胃腸道惡性腫瘤的預(yù)防和治療具有廣闊的應(yīng)用前景，但還有許多問題需進一步研究證實。
結(jié)論 　組蛋白修飾與胃腸道惡性腫瘤的發(fā)生有關(guān)，逆轉(zhuǎn)表觀遺傳修飾導(dǎo)致的基因表達改變對于胃腸道惡性腫瘤的預(yù)防和治療具有重要意義。

引用本文： 孟春風(fēng),戴冬秋. 組蛋白修飾與胃腸道惡性腫瘤的關(guān)系. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(5): 608-611. doi: 復(fù)制

1. 　Wolffe AP, Matzke MA. Epigenetics: regulation through repression [J]. Science， 1999; 286(5439)∶481.
2. 　Feinberg AP, Vogelstein B. Hypomethylation distinguishes ge-nes of some human cancers from their normal counterparts [J]. Nature， 1983; 301(5895)∶89.
3. 　Strahl BD, Allis CD. The language of covalent histone modifications [J]. Nature， 2000; 403(6765)∶41.
4. 　楊少輝， 戴冬秋. 腫瘤抑制基因甲基化與胃癌 [J]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13（5）∶614.
5. 　Rea S, Eisenhaber F, O’Carroll D, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases [J]. Nature， 2000; 406(6796)∶593.
6. 　Jenuwein T, Allis CD. Translating the histone code [J]. Science， 2001; 293(5532)∶1074.
7. 　Wang H, Cao R, Xia L, et al. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase [J]. Mol Cell， 2001; 8(6)∶1207.
8. 　Schubeler D, MacAlpine DM, Scalzo D, et al. The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote [J]. Genes Dev， 2004; 18(11)∶1263.
9. 　Liang G, Lin JC, Wei V, et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome [J]. Proc Natl Acad Sci USA， 2004; 101(19)∶7357.
10. 　Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 [J]. Cell， 2004; 119(7)∶941.
11. 　Mahadevan LC, Willis AC, Barratt MJ. Rapid histone H3 ph-osphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors [J]. Cell， 1991; 65(5)∶775.
12. 　Nowak SJ, Corces VG. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation [J]. Trends Genet， 2004; 20(4)∶214.
13. 　Salvador LM, Park Y, Cottom J, et al. Follicle-stimulating hormone stimulates protein kinase A-mediated histone H3 phosphorylation and acetylation leading to select gene activation in ovarian granulosa cells [J]. J Biol Chem， 2001; 276(43)∶40146.
14. 　Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications [J]. Cell， 2000; 103(2)∶263.
15. 　Nowak SJ, Corces VG. Phosphorylation of histone H3 correlates with transcriptionally active loci [J]. Genes Dev， 2000; 14(23)∶3003.
16. 　Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J]. Nat Genet， 1999; 21(1)∶103.
17. 　Kondo Y, Shen L, Issa JP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer [J]. Mol Cell Biol， 2003; 23(1)∶206.
18. 　Fahrner JA, Eguchi S, Herman JG, et al. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer [J]. Cancer Res， 2002; 62(24)∶7213.
19. 　Fuks F， Hurd PJ， Wolf D， et al. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation [J]. J Biol Chem， 2003; 278(6)∶4035.
20. 　Bachman KE, Park BH, Rhee I, et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene [J]. Cancer Cell， 2003; 3(1)∶89.
21. 　Cheung P, Tanner KG, Cheung WL, et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation [J]. Mol Cell， 2000; 5(6)∶905.
22. 　Lo WS, Trievel RC, Rojas JR, et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14 [J]. Mol Cell， 2000; 5(6)∶917.
23. 　Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails [J]. Genes Dev， 2001; 15(18)∶2343.
24. 　Wang H, Huang ZQ, Xia L, et al. Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor [J]. Science， 2001; 293(5531)∶853.
25. 　Fang JY, Chen YX, Lu J, et al. Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines: Colo-320 and SW1116 [J]. Cell Res， 2004; 14(3)∶217.
26. 　Mitani Y, Oue N, Hamai Y, et al. Histone H3 acetylation is associated with reduced p21(WAF1/CIP1) expression by gastric carcinoma [J]. J Pathol， 2005; 205(1)∶65.
27. 　Hamai Y, Oue N, Mitani Y, et al. DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma [J]. Cancer Sci， 2003; 94(8)∶692.
28. 　Loprevite M, Tiseo M, Grossi F, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines [J]. Oncol Res， 2005; 15(1)∶39.
29. 　Egger G, Liang G, Aparicio A, et al. Epigenetics in human disease and prospects for epigenetic therapy [J]. Nature， 2004; 429(6990)∶457.
30. 　Dobosy JR, Roberts JL, Fu VX, et al. The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia [J]. J Urol， 2007; 177(3)∶822.
31. 　 Kaminskas E, Farrell A, Abraham S, et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes [J]. Clin Cancer Res, 2005; 11(10)∶3604.
  1. 1. 　Wolffe AP, Matzke MA. Epigenetics: regulation through repression [J]. Science， 1999; 286(5439)∶481.
  2. 2. 　Feinberg AP, Vogelstein B. Hypomethylation distinguishes ge-nes of some human cancers from their normal counterparts [J]. Nature， 1983; 301(5895)∶89.
  3. 3. 　Strahl BD, Allis CD. The language of covalent histone modifications [J]. Nature， 2000; 403(6765)∶41.
  4. 4. 　楊少輝， 戴冬秋. 腫瘤抑制基因甲基化與胃癌 [J]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13（5）∶614.
  5. 5. 　Rea S, Eisenhaber F, O’Carroll D, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases [J]. Nature， 2000; 406(6796)∶593.
  6. 6. 　Jenuwein T, Allis CD. Translating the histone code [J]. Science， 2001; 293(5532)∶1074.
  7. 7. 　Wang H, Cao R, Xia L, et al. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase [J]. Mol Cell， 2001; 8(6)∶1207.
  8. 8. 　Schubeler D, MacAlpine DM, Scalzo D, et al. The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote [J]. Genes Dev， 2004; 18(11)∶1263.
  9. 9. 　Liang G, Lin JC, Wei V, et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome [J]. Proc Natl Acad Sci USA， 2004; 101(19)∶7357.
  10. 10. 　Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 [J]. Cell， 2004; 119(7)∶941.
  11. 11. 　Mahadevan LC, Willis AC, Barratt MJ. Rapid histone H3 ph-osphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors [J]. Cell， 1991; 65(5)∶775.
  12. 12. 　Nowak SJ, Corces VG. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation [J]. Trends Genet， 2004; 20(4)∶214.
  13. 13. 　Salvador LM, Park Y, Cottom J, et al. Follicle-stimulating hormone stimulates protein kinase A-mediated histone H3 phosphorylation and acetylation leading to select gene activation in ovarian granulosa cells [J]. J Biol Chem， 2001; 276(43)∶40146.
  14. 14. 　Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications [J]. Cell， 2000; 103(2)∶263.
  15. 15. 　Nowak SJ, Corces VG. Phosphorylation of histone H3 correlates with transcriptionally active loci [J]. Genes Dev， 2000; 14(23)∶3003.
  16. 16. 　Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J]. Nat Genet， 1999; 21(1)∶103.
  17. 17. 　Kondo Y, Shen L, Issa JP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer [J]. Mol Cell Biol， 2003; 23(1)∶206.
  18. 18. 　Fahrner JA, Eguchi S, Herman JG, et al. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer [J]. Cancer Res， 2002; 62(24)∶7213.
  19. 19. 　Fuks F， Hurd PJ， Wolf D， et al. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation [J]. J Biol Chem， 2003; 278(6)∶4035.
  20. 20. 　Bachman KE, Park BH, Rhee I, et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene [J]. Cancer Cell， 2003; 3(1)∶89.
  21. 21. 　Cheung P, Tanner KG, Cheung WL, et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation [J]. Mol Cell， 2000; 5(6)∶905.
  22. 22. 　Lo WS, Trievel RC, Rojas JR, et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14 [J]. Mol Cell， 2000; 5(6)∶917.
  23. 23. 　Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails [J]. Genes Dev， 2001; 15(18)∶2343.
  24. 24. 　Wang H, Huang ZQ, Xia L, et al. Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor [J]. Science， 2001; 293(5531)∶853.
  25. 25. 　Fang JY, Chen YX, Lu J, et al. Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines: Colo-320 and SW1116 [J]. Cell Res， 2004; 14(3)∶217.
  26. 26. 　Mitani Y, Oue N, Hamai Y, et al. Histone H3 acetylation is associated with reduced p21(WAF1/CIP1) expression by gastric carcinoma [J]. J Pathol， 2005; 205(1)∶65.
  27. 27. 　Hamai Y, Oue N, Mitani Y, et al. DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma [J]. Cancer Sci， 2003; 94(8)∶692.
  28. 28. 　Loprevite M, Tiseo M, Grossi F, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines [J]. Oncol Res， 2005; 15(1)∶39.
  29. 29. 　Egger G, Liang G, Aparicio A, et al. Epigenetics in human disease and prospects for epigenetic therapy [J]. Nature， 2004; 429(6990)∶457.
  30. 30. 　Dobosy JR, Roberts JL, Fu VX, et al. The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia [J]. J Urol， 2007; 177(3)∶822.
  31. 31. 　 Kaminskas E, Farrell A, Abraham S, et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes [J]. Clin Cancer Res, 2005; 11(10)∶3604.