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Gene Review

Apc  -  adenomatosis polyposis coli

Mus musculus

Synonyms: AI047805, AU020952, AW124434, Adenomatous polyposis coli protein, CC1, ...
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Disease relevance of Apc

  • Furthermore, treating Apc delta716 mice with a novel COX-2 inhibitor reduced the polyp number more significantly than with sulindac, which inhibits both isoenzymes [1].
  • Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2) [1].
  • Expression profiling of wildtype and Apc-mutated teratomas supports the differentiation defects at the molecular level and pinpoints a large number of downstream structural and regulating genes [2].
  • Various Apc knockout mice, including the multiple intestinal neoplasia (Min) mouse and the Apc(Delta716) mouse, are limited by their lack of large numbers of colonic adenomas and aberrant crypt foci, the putative precursors of large-bowel polyps and cancers [3].
  • To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis [4].

Psychiatry related information on Apc

  • The broad-spectrum MMP inhibitor (A-177430; MMPI) and the selective COX-2 inhibitor (A-285969; COX-2I) both showed dose-dependent inhibition of the number of adenomas in Min mice [5].

High impact information on Apc

  • The demonstration that, in the C57BL/6 (B6) Apc(Min/+) mouse model of inherited intestinal cancer, loss of Apc function can occur by loss of heterozygosity (LOH) through somatic recombination between homologs presents an opportunity to search for polymorphisms in the homologous somatic recombination pathway [6].
  • As the copy number of Rb9 increases, the association with the interphase nucleolus of the rDNA repeats centromeric to the Apc locus on Chromosome 18 is increasingly disrupted [6].
  • Our results imply that constitutive activation of the Apc/beta-catenin signaling pathway results in differentiation defects in tissue homeostasis, and possibly underlies tumorigenesis in the colon and other self-renewing tissues [2].
  • We provide genetic and molecular evidence that the ability and sensitivity of ES cells to differentiate into the three germ layers is inhibited by increased doses of beta-catenin by specific Apc mutations [2].
  • The adenomatous polyposis coli gene (APC) is a major controller of the Wnt pathway and is essential to prevent tumorigenesis in a variety of tissues and organs [2].

Chemical compound and disease context of Apc

  • Nimesulide, a COX-2 selective inhibitor used as positive control, showed similar suppressive effects on the development of ACFs in AOM-treated rats and polyps in Apc gene knockout mice [7].
  • When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose [7].
  • Combined treatment of mice with piroxicam plus DFMO was much more effective than either agent alone and resulted in a significant number of mice totally free of any intestinal adenomas (P < 0.001), in contrast to the 100% incidence and high multiplicity in control Min mice [8].
  • Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos [8].
  • Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice [9].

Biological context of Apc


Anatomical context of Apc


Associations of Apc with chemical compounds


Physical interactions of Apc


Co-localisations of Apc


Regulatory relationships of Apc

  • The multiplicity and invasiveness of intestinal adenomas of Apc(Min/+) (Min) mice was enhanced by deficiency for p53 [13].
  • However, in Msh3(-/-)Msh6(-/-)Apc1638N tumors, we observed a mixture of base substitutions (46%) and frameshifts (54%), indicating that in Msh6(-/-)Apc1638N mice frameshift mutations in the Apc gene were suppressed by Msh3 [27].
  • Msh2 deficiency enhances somatic Apc and p53 mutations in Apc+/-Msh2-/- mice [28].
  • CONCLUSIONS: Introduction of the E-cadherin mutation in Apc1638N animals enhances Apc-driven tumor initiation without clearly affecting tumor progression [29].
  • Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control [11].

Other interactions of Apc

  • Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon [11].
  • Mom1 is a semidominant modifier of polyp size and multiplicity in Min mice (Gould and Dove 1997), and encodes the secretory type II nonpancreatic phospholipase A2 (Pla2g2a) gene (MacPhee et al. 1995; Cornier et al. 1997, 2000) [14].
  • Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice [30].
  • Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia [14].
  • Apc mutations in Msh6(-/-)Apc1638N mice consisted predominantly of base substitutions (93%) creating stop codons, consistent with a major role for Msh6 in the repair of base-base mismatches [27].

Analytical, diagnostic and therapeutic context of Apc


  1. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Oshima, M., Dinchuk, J.E., Kargman, S.L., Oshima, H., Hancock, B., Kwong, E., Trzaskos, J.M., Evans, J.F., Taketo, M.M. Cell (1996) [Pubmed]
  2. Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling. Kielman, M.F., Rindapää, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M.M., Roberts, S., Smits, R., Fodde, R. Nat. Genet. (2002) [Pubmed]
  3. Suppression of intestinal polyps in Msh2-deficient and non-Msh2-deficient multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Lal, G., Ash, C., Hay, K., Redston, M., Kwong, E., Hancock, B., Mak, T., Kargman, S., Evans, J.F., Gallinger, S. Cancer Res. (2001) [Pubmed]
  4. Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps. Seno, H., Oshima, M., Ishikawa, T.O., Oshima, H., Takaku, K., Chiba, T., Narumiya, S., Taketo, M.M. Cancer Res. (2002) [Pubmed]
  5. Cooperative effects of matrix metalloproteinase and cyclooxygenase-2 inhibition on intestinal adenoma reduction. Wagenaar-Miller, R.A., Hanley, G., Shattuck-Brandt, R., DuBois, R.N., Bell, R.L., Matrisian, L.M., Morgan, D.W. Br. J. Cancer (2003) [Pubmed]
  6. A Robertsonian translocation suppresses a somatic recombination pathway to loss of heterozygosity. Haigis, K.M., Dove, W.F. Nat. Genet. (2003) [Pubmed]
  7. Inhibitory effects of mofezolac, a cyclooxygenase-1 selective inhibitor, on intestinal carcinogenesis. Kitamura, T., Kawamori, T., Uchiya, N., Itoh, M., Noda, T., Matsuura, M., Sugimura, T., Wakabayashi, K. Carcinogenesis (2002) [Pubmed]
  8. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Jacoby, R.F., Cole, C.E., Tutsch, K., Newton, M.A., Kelloff, G., Hawk, E.T., Lubet, R.A. Cancer Res. (2000) [Pubmed]
  9. Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice. Nakatsugi, S., Fukutake, M., Takahashi, M., Fukuda, K., Isoi, T., Taniguchi, Y., Sugimura, T., Wakabayashi, K. Jpn. J. Cancer Res. (1997) [Pubmed]
  10. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Takaku, K., Oshima, M., Miyoshi, H., Matsui, M., Seldin, M.F., Taketo, M.M. Cell (1998) [Pubmed]
  11. Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon. Perreault, N., Sackett, S.D., Katz, J.P., Furth, E.E., Kaestner, K.H. Genes Dev. (2005) [Pubmed]
  12. Apc1638N: a mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cysts. Smits, R., van der Houven van Oordt, W., Luz, A., Zurcher, C., Jagmohan-Changur, S., Breukel, C., Khan, P.M., Fodde, R. Gastroenterology (1998) [Pubmed]
  13. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers. Halberg, R.B., Katzung, D.S., Hoff, P.D., Moser, A.R., Cole, C.E., Lubet, R.A., Donehower, L.A., Jacoby, R.F., Dove, W.F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  14. Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia. Silverman, K.A., Koratkar, R., Siracusa, L.D., Buchberg, A.M. Genome Res. (2002) [Pubmed]
  15. Progressive changes in adherens junction structure during intestinal adenoma formation in Apc mutant mice. Carothers, A.M., Melstrom, K.A., Mueller, J.D., Weyant, M.J., Bertagnolli, M.M. J. Biol. Chem. (2001) [Pubmed]
  16. Dysregulated expression of beta-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice. Kongkanuntn, R., Bubb, V.J., Sansom, O.J., Wyllie, A.H., Harrison, D.J., Clarke, A.R. Oncogene (1999) [Pubmed]
  17. Cells heterozygous for the ApcMin mutation have decreased gap junctional intercellular communication and connexin43 level, and reduced microtubule polymerization. Husøy, T., Cruciani, V., Knutsen, H.K., Mikalsen, S.O., Ølstørn, H.B., Alexander, J. Carcinogenesis (2003) [Pubmed]
  18. Modulation of tumor formation and intestinal cell migration by estrogens in the Apc(Min/+) mouse model of colorectal cancer. Javid, S.H., Moran, A.E., Carothers, A.M., Redston, M., Bertagnolli, M.M. Carcinogenesis (2005) [Pubmed]
  19. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Jacoby, R.F., Seibert, K., Cole, C.E., Kelloff, G., Lubet, R.A. Cancer Res. (2000) [Pubmed]
  20. Apc deficiency is associated with increased Egfr activity in the intestinal enterocytes and adenomas of C57BL/6J-Min/+ mice. Moran, A.E., Hunt, D.H., Javid, S.H., Redston, M., Carothers, A.M., Bertagnolli, M.M. J. Biol. Chem. (2004) [Pubmed]
  21. Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity. Choi, H.J., Huber, A.H., Weis, W.I. J. Biol. Chem. (2006) [Pubmed]
  22. Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP kinase and APC complex activation. Hildesheim, J., Belova, G.I., Tyner, S.D., Zhou, X., Vardanian, L., Fornace, A.J. Oncogene (2004) [Pubmed]
  23. Emergent issues in the genetics of intestinal neoplasia. Dove, W.F., Gould, K.A., Luongo, C., Moser, A.R., Shoemaker, A.R. Cancer Surv. (1995) [Pubmed]
  24. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Wen, Y., Eng, C.H., Schmoranzer, J., Cabrera-Poch, N., Morris, E.J., Chen, M., Wallar, B.J., Alberts, A.S., Gundersen, G.G. Nat. Cell Biol. (2004) [Pubmed]
  25. The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Erdmann, K.S., Kuhlmann, J., Lessmann, V., Herrmann, L., Eulenburg, V., Müller, O., Heumann, R. Oncogene (2000) [Pubmed]
  26. The tumor suppressor protein APC colocalizes with beta-catenin in the colon epithelial cells. Senda, T., Miyashiro, I., Matsumine, A., Baeg, G.H., Monden, T., Kobayashil, S., Monden, M., Toyoshima, K., Akiyama, T. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  27. The distinct spectra of tumor-associated Apc mutations in mismatch repair-deficient Apc1638N mice define the roles of MSH3 and MSH6 in DNA repair and intestinal tumorigenesis. Kuraguchi, M., Yang, K., Wong, E., Avdievich, E., Fan, K., Kolodner, R.D., Lipkin, M., Brown, A.M., Kucherlapati, R., Edelmann, W. Cancer Res. (2001) [Pubmed]
  28. Msh2 deficiency enhances somatic Apc and p53 mutations in Apc+/-Msh2-/- mice. Sohn, K.J., Choi, M., Song, J., Chan, S., Medline, A., Gallinger, S., Kim, Y.I. Carcinogenesis (2003) [Pubmed]
  29. E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in mice. Smits, R., Ruiz, P., Diaz-Cano, S., Luz, A., Jagmohan-Changur, S., Breukel, C., Birchmeier, C., Birchmeier, W., Fodde, R. Gastroenterology (2000) [Pubmed]
  30. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Chulada, P.C., Thompson, M.B., Mahler, J.F., Doyle, C.M., Gaul, B.W., Lee, C., Tiano, H.F., Morham, S.G., Smithies, O., Langenbach, R. Cancer Res. (2000) [Pubmed]
  31. Truncated mouse adenomatous polyposis coli reduces connexin32 content and increases matrilysin secretion from Paneth cells. Husøy, T., Ølstørn, H.B., Knutsen, H.K., Løberg, E.M., Cruciani, V., Mikalsen, S.O., Goverud, I.L., Alexander, J. Eur. J. Cancer (2004) [Pubmed]
  32. Elevated cyclooxygenase-2 levels in Min mouse adenomas. Williams, C.S., Luongo, C., Radhika, A., Zhang, T., Lamps, L.W., Nanney, L.B., Beauchamp, R.D., DuBois, R.N. Gastroenterology (1996) [Pubmed]
  33. Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min/+) mice. Hansen-Petrik, M.B., McEntee, M.F., Jull, B., Shi, H., Zemel, M.B., Whelan, J. Cancer Res. (2002) [Pubmed]
  34. Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522. Sasai, H., Masaki, M., Wakitani, K. Carcinogenesis (2000) [Pubmed]
  35. Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene. Hasegawa, S., Sato, T., Akazawa, H., Okada, H., Maeno, A., Ito, M., Sugitani, Y., Shibata, H., Miyazaki Ji, J., Katsuki, M., Yamauchi, Y., Yamamura Ki, K., Katamine, S., Noda, T. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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