• 四川大學(xué)華西醫(yī)院普外科（成都 610041）;

目的 　探討T細(xì)胞因子-4（T cell factor-4,TCF-4）在調(diào)控大腸癌形成中的作用。
方法 　收集近年來(lái)國(guó)內(nèi)、外有關(guān)研究TCF-4與結(jié)直腸癌形成機(jī)理的文獻(xiàn)并作一綜述。
結(jié)果 　對(duì)于TCF-4基因，不同的剪接形式產(chǎn)生不同的異構(gòu)體，編碼不同的蛋白質(zhì)。TCF-4蛋白為序列特異的DNA結(jié)合蛋白，不能獨(dú)立激活或抑制轉(zhuǎn)錄，需通過(guò)其多個(gè)結(jié)構(gòu)域與不同的配體發(fā)生相互作用，從而產(chǎn)生不同的效應(yīng)。
結(jié)論 　TCF-4被視為將其他輔助蛋白質(zhì)靶定于一組確切啟動(dòng)子的核傳播媒介，在調(diào)控大腸癌的形成中起著分子開(kāi)關(guān)的作用。

引用本文： 孟文建,李立,周總光. 調(diào)控大腸癌形成的分子開(kāi)關(guān)——T細(xì)胞因子-4. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(10): 787-789. doi: 復(fù)制

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2. 　Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling [J]. Cell, 2000; 103(2)∶311.
3. 　Pukrop T, Gradl D, Henningfeld KA, et al. Identification of two regulatory elements within the high mobility group box transcription factor XTCF-4 [J]. J Biol Chem, 2001; 276(12)∶ 8968.
4. 　Valenta T, Lukas J, Korinek V. HMG box transcription factor TCF-4’s interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells [J]. Nucleic Acids Res, 2003; 31(9)∶2369.
5. 　Duval A, Busson-Leconiat M, Berger R, et al. Assignment of the TCF-4 (TCF7L2) gene to human chromosome band 10q25.3 [J]. Cytogenet Cell Genet, 2000; 88(3-4)∶264.
6. 　Shiina H, Igawa M, Breault J, et al. The human T-cell factor-4 gene splicing isoforms, Wnt signal pathway, and apoptosis in renal cell carcinoma [J]. Clin Cancer Res, 2003; 9(6)∶2121.
7. 　Howng SL, Huang FH, Hwang SL, et al. Differential expression and splicing isoform analysis of human Tcf-4 transcription factor in brain tumors [J]. Int J Oncol, 2004; 25(6)∶1685.
8. 　Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J]. Nat Genet, 2006; 38(3)∶320.
9. 　Sparks AB, Morin PJ, Vogelstein B, et al. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer [J]. Cancer Res, 1998; 58(6)∶1130.
10. 　Duval A, Rolland S, Tubacher E, et al. The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines [J]. Cancer Res, 2000; 60(14)∶3872.
11. 　Van de Wetering M, Castrop J, Korinek V, et al. Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties[J]. Mol Cell Biol, 1996; 16(3)∶745.
12. 　Hovanes K, Li TW, Waterman ML. The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing[J]. Nucleic Acids Res, 2000; 28(9)∶1994.
13. 　Lee YJ, Swencki B, Shoichet S, et al. A possible role for the high mobility group box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation[J]. J Biol Chem, 1999; 274(3)∶1566.
14. 　Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma[J]. Science, 1997; 275(5307)∶1784.
15. 　Graham TA, Weaver C, Mao F, et al. Crystal structure of a beta-catenin/Tcf complex[J]. Cell, 2000; 103(6)∶885.
16. 　Hurlstone A, Clevers H. T-cell factors: turn-ons and turn-offs[J]. EMBO J, 2002; 21(10)∶2303.
17. 　Fasolini M, Wu XQ, Flocco M, et al. Hot spots in Tcf4 for the interaction with beta-catenin[J]. J Biol Chem, 2003; 278(23)∶21092.
18. 　Barker N, Huls G, Korinek V, et al. Restricted high level expression of Tcf4 protein in intestinal and mammary gland epithelium [J]. Am J Path, 1999; 154(1)∶29.
19. 　Korinek V, Barker N, Moerer P, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4[J]. Nat Genet, 1998; 19(4)∶379.
20. 　Muncan V, Faro A, Haramis AP, et al. T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine[J]. EMBO Rep, 2007; 8(10)∶966.
21. 　Cui J, Zhou X, Liu Y, et al. Wnt signaling in hepatocellular carcinoma： analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes[J]. J Gastroenterol Hepatol, 2003; 18(3)∶280.
22. 　Zhao DH, Hong JJ, Guo SY, et al. Aberrant expression and function of TCF-4 in the proliferation of hepatocellular carcinoma cell line BEL-7402[J]. Cell Res, 2004; 14(1)∶74.
23. 　Li CY, Wang Y, Cui ZS, et al. Expression of T cell factor-4 in non-small-cell lung cancer [J]. Chin Med J (Engl), 2005; 118(2)∶136.
24. 　Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer[J]. Biochim Biophys Acta, 2003; 1653(1)∶1.
  1. 1. 24　Roose J, Clevers H. TCF transcription factors: molecular switches in carcinogenesis[J]. Biochim Biophys Acta, 1999; 1424(2-3)∶M23 25　Thorstensen L, Lind GE, Lvig T, et al. Genetic and epigenetic changes of components affecting the WNT pathway in colorectal carcinomas stratified by microsatellite instability[J]. Neoplasia, 2005; 7(2)∶99 26　Duval A, Gayet J, Zhou XP, et al. Frequent frameshift mutations of the TCF-4 gene in colorectal cancers with microsatellite instability[J]. Cancer Res, 1999; 59(17)∶4213 27　Collins RT, Treisman JE. Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes[J]. Genes Dev, 2000; 14(24)∶3140 28　Chang HR, Cheng TL, Liu TZ, et al. Gentic and cellular characterizations of human TCF4 with microsatellite instability in colon cancer and leukemia cell lines[J]. Cancer Lett, 2005; 233(1)∶165 29　Ruckert S, Hiendlmeyer E, Brueckl WM, et al. T-cell factor-4 frameshift mutations occur frequently in human microsatellite instability-high colorectal carcinomas but do not contribute to carcinogenesis[J]. Cancer Res, 2002; 62(11)∶3009 30　Zhang L, Yu J, Willson JK, et al. Short mononucleotide repeat sequence variability in mismatch repair-deficient cancers[J]. Cancer Res, 2001; 61(9)∶3801 31　Meng WJ, Wang L, Tian C, et al. Novel mutations and sequence variants in exon 3-9 of human T cell factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability[J]. World J Gastroenterol, 2007; 13(27)∶3747 32　Omer CA, Miller PJ, Diehl RE, et al. Identification of Tcf-4 residues involved in high affinity beta-catenin binding[J]. Biochem Biophys Res Commun, 1999; 256(3)∶584.
  2. 2. 　Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling [J]. Cell, 2000; 103(2)∶311.
  3. 3. 　Pukrop T, Gradl D, Henningfeld KA, et al. Identification of two regulatory elements within the high mobility group box transcription factor XTCF-4 [J]. J Biol Chem, 2001; 276(12)∶ 8968.
  4. 4. 　Valenta T, Lukas J, Korinek V. HMG box transcription factor TCF-4’s interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells [J]. Nucleic Acids Res, 2003; 31(9)∶2369.
  5. 5. 　Duval A, Busson-Leconiat M, Berger R, et al. Assignment of the TCF-4 (TCF7L2) gene to human chromosome band 10q25.3 [J]. Cytogenet Cell Genet, 2000; 88(3-4)∶264.
  6. 6. 　Shiina H, Igawa M, Breault J, et al. The human T-cell factor-4 gene splicing isoforms, Wnt signal pathway, and apoptosis in renal cell carcinoma [J]. Clin Cancer Res, 2003; 9(6)∶2121.
  7. 7. 　Howng SL, Huang FH, Hwang SL, et al. Differential expression and splicing isoform analysis of human Tcf-4 transcription factor in brain tumors [J]. Int J Oncol, 2004; 25(6)∶1685.
  8. 8. 　Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J]. Nat Genet, 2006; 38(3)∶320.
  9. 9. 　Sparks AB, Morin PJ, Vogelstein B, et al. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer [J]. Cancer Res, 1998; 58(6)∶1130.
  10. 10. 　Duval A, Rolland S, Tubacher E, et al. The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines [J]. Cancer Res, 2000; 60(14)∶3872.
  11. 11. 　Van de Wetering M, Castrop J, Korinek V, et al. Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties[J]. Mol Cell Biol, 1996; 16(3)∶745.
  12. 12. 　Hovanes K, Li TW, Waterman ML. The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing[J]. Nucleic Acids Res, 2000; 28(9)∶1994.
  13. 13. 　Lee YJ, Swencki B, Shoichet S, et al. A possible role for the high mobility group box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation[J]. J Biol Chem, 1999; 274(3)∶1566.
  14. 14. 　Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma[J]. Science, 1997; 275(5307)∶1784.
  15. 15. 　Graham TA, Weaver C, Mao F, et al. Crystal structure of a beta-catenin/Tcf complex[J]. Cell, 2000; 103(6)∶885.
  16. 16. 　Hurlstone A, Clevers H. T-cell factors: turn-ons and turn-offs[J]. EMBO J, 2002; 21(10)∶2303.
  17. 17. 　Fasolini M, Wu XQ, Flocco M, et al. Hot spots in Tcf4 for the interaction with beta-catenin[J]. J Biol Chem, 2003; 278(23)∶21092.
  18. 18. 　Barker N, Huls G, Korinek V, et al. Restricted high level expression of Tcf4 protein in intestinal and mammary gland epithelium [J]. Am J Path, 1999; 154(1)∶29.
  19. 19. 　Korinek V, Barker N, Moerer P, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4[J]. Nat Genet, 1998; 19(4)∶379.
  20. 20. 　Muncan V, Faro A, Haramis AP, et al. T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine[J]. EMBO Rep, 2007; 8(10)∶966.
  21. 21. 　Cui J, Zhou X, Liu Y, et al. Wnt signaling in hepatocellular carcinoma： analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes[J]. J Gastroenterol Hepatol, 2003; 18(3)∶280.
  22. 22. 　Zhao DH, Hong JJ, Guo SY, et al. Aberrant expression and function of TCF-4 in the proliferation of hepatocellular carcinoma cell line BEL-7402[J]. Cell Res, 2004; 14(1)∶74.
  23. 23. 　Li CY, Wang Y, Cui ZS, et al. Expression of T cell factor-4 in non-small-cell lung cancer [J]. Chin Med J (Engl), 2005; 118(2)∶136.
  24. 24. 　Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer[J]. Biochim Biophys Acta, 2003; 1653(1)∶1.