Abstract
Genetic analysis of β-catenin-induced oncogenic transformation in chicken embryo fibroblasts (CEF) revealed the following prerequisites for oncogenicity: (1) removal of the N terminal phosphorylation sites targeted by glycogen synthase kinase 3β (GSK3β), (2) retention of the N terminal transactivation domain, and (3) retention of the armadillo repeats. The C terminal transactivation domain played an ancillary role in the transformation of CEF. There was a rough correlation between the transforming activity of various β-catenin constructs and their transactivation of the TOPFLASH reporter. Expression levels of the candidate target genes of β-catenin-LEF, cyclin D1 and myc were not correlated with each other or with the transforming activity of β-catenin constructs. A new target gene, coding for inositol hexakisphosphate kinase 2 (IP6K2) was identified. Its expression showed concordance with the transforming activity of β-catenin constructs.
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References
Aoki M, Batista O, Bellacosa A, Tsichlis P, Vogt PK . 1998 Proc. Natl. Acad. Sci. USA 95: 14950–14955
Aoki M, Hecht A, Kruse U, Kemler R, Vogt PK . 1999 Proc. Natl. Acad. Sci. USA 96: 139–144
Barth AI, Stewart DB, Nelson WJ . 1999 Proc. Natl. Acad. Sci. USA 96: 4947–4952
Bienz M, Clevers H . 2000 Cell 103: 311–320
Dahmen RP, Koch A, Denkhaus D, Tonn JC, Sorensen N, Berthold F, Behrens J, Birchmeier W, Wiestler OD, Pietsch T . 2001 Cancer Res. 61: 7039–7043
Eastman Q, Grosschedl R . 1999 Curr. Opin. Cell Biol. 11: 233–240
Fu S, Bottoli I, Goller M, Vogt PK . 1999 Proc. Natl. Acad. Sci. USA 96: 5716–5721
Guger KA, Gumbiner BM . 2000 Dev. Biol. 223: 441–448
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW . 1998 Science 281: 1509–1512
Hecht A, Litterst CM, Huber O, Kemler R . 1999 J. Biol. Chem. 274: 18017–18025
Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R . 2000 EMBO J. 19: 1839–1850
Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X . 2002 Cell 108: 837–847
Kawai S, Nishizawa M . 1984 Mol. Cell. Biol. 4: 1172–1174
Kolligs FT, Hu G, Dang CV, Fearon ER . 1999 Mol. Cell. Biol. 19: 5696–5706
Kruse U, Iacovoni JS, Goller ME, Vogt PK . 1997 Proc. Natl. Acad. Sci. USA 94: 12396–12400
Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, Halling KC, Cunningham JM, Boardman LA, Qian C, Christensen E, Schmidt SS, Roche PC, Smith DI, Thibodeau SN . 2000 Nat. Genet. 26: 146–147
Miller JR, Hocking AM, Brown JD, Moon RT . 1999 Oncogene 18: 7860–7872
Morin PJ . 1999 Bioessays 21: 1021–1030
Morisson BH, Bauer JA, Kalvakolanu DV, Lindner DJ . 2001 J. Biol. Chem. 276: 24965–24970
Nagasawa Y, Miyoshi Y, Iwao K, Shinomura Y, Matsuzawa Y, Nakamura Y . 1999 Cancer Res. 59: 3539–3542
Norbis F, Boll M, Stange G, Markovich D, Verrey F, Biber J, Murer H . 1997 J. Memb. Biol. 156: 19–24
Nusse R, Varmus HE . 1992 Cell 69: 1073–1087
Orford K, Orford CC, Byers SW . 1999 J. Cell. Biol. 146: 855–868
Peifer M, Polakis P . 2000 Science 287: 1606–1609
Polakis P . 1999 Curr. Opin. Genet. Dev. 9: 15–21
Polakis P . 2000 Genes Dev. 14: 1837–1851
Safrany ST, Caffrey JJ, Yang X, Shears SB . 1999 Biol. Chem. 380: 945–951
Saiardi A, Erdjument-Bromage H, Snowman AM, Tempst P, Snyder SH . 1999 Curr. Biol. 9: 1323–1326
Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y . 2000 Nat. Genet. 24: 245–250
Schell MJ, Letcher AJ, Brearley CA, Biber J, Murer H, Irvine RF . 1999 FEBS Lett. 461: 169–172
Shamsuddin AM . 1999 Anticancer Res. 19: 3733–3736
Shamsuddin AM, Vucenik I . 1999 Anticancer Res. 19: 3671–3674
Staal FJ, Noort MVM, Strous GJ, Clevers HC . 2002 EMBO Rep. 3: 63–68
Sun Y, Kolligs FT, Hottiger MO, Mosavin R, Fearon ER, Nabel GJ . 2000 Proc. Natl. Acad. Sci. USA 97: 12613–12618
Takemaru KI, Moon RT . 2000 J. Cell. Biol. 149: 249–254
Tetsu O, McCormick F . 1999 Nature 398: 422–426
Vleminckx K, Kemler R, Hecht A . 1999 Mech. Dev. 81: 65–74
Vogt PK . 2001 Oncogene 20: 2365–2377
Vucenik I, Tantivejkul K, Zhang ZS, Cole KE, Saied I, Shamsuddin AM . 1998a Anticancer Res. 18: 4083–4090
Vucenik I, Zhang ZS, Shamsuddin AM . 1998b Anticancer Res. 18: 4091–4096
Whitehead I, Kirk H, Kay R . 1995 Mol. Cell. Biol. 15: 704–710
Willert K, Nusse R . 1998 Curr. Opin. Genet. Dev. 8: 95–102
Young CS, Kitamura M, Hardy S, Kitajewski J . 1998 Mol. Cell. Biol. 18: 2474–2485
Acknowledgements
This work was supported by NIH research grants CA 79616 and CA 78230. This is manuscript number 14600-MEM of the Department of Molecular and Experimental Medicine, The Scripps Research Institute.
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Aoki, M., Sobek, V., Maslyar, D. et al. Oncogenic transformation by β-catenin: deletion analysis and characterization of selected target genes. Oncogene 21, 6983–6991 (2002). https://doi.org/10.1038/sj.onc.1205796
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DOI: https://doi.org/10.1038/sj.onc.1205796
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