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  • Original Paper
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c-Myb is critical for murine colon development

Oncogene volume 18, pages 5821–5830 (1999)Cite this article

Abstract

The mammalian colon develops from a simple tube of undifferentiated cells into a complex, highly ordered organ, with a continuously self-renewing epithelial layer. We have previously described c-Myb expression in the epithelia of murine and human colon crypts and documented increased expression in colorectal adenocarcinoma cells. To investigate the role of c-Myb in colonic epithelium development, we have used embryos with a disrupted c-myb gene. Prior to the in utero death of these embryos at E15, we excised colon tissue and transplanted it under the kidney capsule of recipient mice to allow further development and cyto-differentiation. Compared to the colons of wildtype and heterozygous littermates, the c-myb homozygous knockout colon is highly irregular with a disordered epithelium and abnormal crypts. In addition, the expression of Bcl-2, a known target of c-Myb, is reduced and apoptosis is increased, indicating a critical requirement for c-Myb in normal colon development.

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References

  • Alitalo K, Winqvist R, Lin CC, de la Chapelle A, Schwab M and Bishop JM. . 1984 Proc. Natl. Acad. Sci. USA 81: 4534–4538.

  • Badiani P, Corbella P, Kioussis D, Marvel J and Weston K. . 1994 Genes Dev. 8: 770–782.

  • Baribault H, Penner J, Iozzo RV and Wilson-Heiner M. . 1994 Genes Dev. 8: 2964–2973.

  • Bedi A, Pasricha PJ, Akhtar AJ, Barber JP, Bedi GC, Giardiello FM, Zehnbauer BA, Hamilton SR and Jones RJ. . 1995 Cancer Res. 55: 1811–1816.

  • Calabretta B and Gewirtz AM. . 1991 Crit. Rev. Oncog. 2: 187–194.

  • Chawengsaksophak K, James R, Hammond VE, Kontgen F and Beck F. . 1997 Nature 386: 84–87.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Frampton J, Ramqvist T and Graf T. . 1996 Genes Dev. 10: 2720–2731.

  • Gabriel A, Robinson PM and Whitehead RH. . 1992 Anat. Rec. 234: 281–290.

  • Gavrieli Y, Sherman Y and Ben-Sasson SA. . 1992 J. Cell Biol. 119: 493–501.

  • Gordon JI and Hermiston ML. . 1994 Curr. Opin. Cell Biol. 6: 795–803.

  • Hague A, Moorghen M, Hicks D, Chapman M and Paraskeva C. . 1994 Oncogene 9: 3367–3370.

  • Hall PA, Coates PJ, Ansari B and Hopwood D. . 1994 J. Cell Sci. 107: 3569–3577.

  • Hermiston ML, Wong MH and Gordon JI. . 1996 Genes Dev. 10: 985–996.

  • Hockenbery DM, Zutter M, Hickey W, Nahm M and Korsmeyer SJ. . 1991 Proc. Natl. Acad. Sci. USA 88: 6961–6965.

  • Hogg A, Schirm S, Nakagoshi H, Bartley P, Ishii S, Bishop JM and Gonda TJ. . 1997 Oncogene 15: 2885–2898.

  • Iwanaga T. . 1995 Arch. Histol. Cytol. 58: 151–159.

  • Kaestner KH, Silberg DG, Traber PG and Schutz G. . 1997 Genes Dev. 11: 1583–1595.

  • Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T, Kitamura Y, Kondoh H and Tsujimoto Y. . 1995 Cancer Res. 55: 354–359.

  • Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M, Wendling C, Tomasetto C, Chambon P and Rio MC. . 1996 Science 274: 259–262.

  • Lu QL, Poulsom R, Wong L and Hanby AM. . 1993 J. Pathol. 169: 431–437.

  • Lyon J, Robinson C and Watson R. . 1994 Crit. Rev. Onco. 5: 373–388.

  • Mashimo H, Wu DC, Podolsky DK and Fishman MC. . 1996 Science 274: 262–265.

  • McMahon J, Howe KM and Watson RJ. . 1988 Oncogene 3: 717–720.

  • Melani C, Rivoltini L, Parmiani G, Calabretta B and Colombo MP. . 1991 Cancer Res. 51: 2897–2901.

  • Merritt AJ, Potten CS, Watson AJ, Loh DY, Nakayama K and Hickman JA. . 1995 J. Cell Sci. 108: 2261–2271.

  • Mucenski ML, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott Jr WJ and Potter SS. . 1991 Cell 65: 677–689.

  • Nakayama K, Negishi I, Kuida K, Sawa H and Loh DY. . 1994 Proc. Natl. Acad. Sci. USA 91: 3700–3704.

  • Novack DV and Korsmeyer SJ. . 1994 Am. J. Pathol. 145: 61–73.

  • Potten CS. . 1992 Cancer Metastasis Rev. 11: 179–195.

  • Potten CS, Kellett M, Roberts SA, Rew DA and Wilson GD. . 1992 Gut 33: 71–78.

  • Ramsay RG, Thompson MA, Hayman JA, Reid G, Gonda TJ and Whitehead RH. . 1992 Cell Growth Differ. 3: 723–730.

  • Reed JC. . 1997 Semin. Hematol. 34: 9–19.

  • Resnik E. . 1997 Nat. Genet. 16: 9–11.

  • Rosenthal MA, Thompson MA, Ellis S, Whitehead RH and Ramsay RG. . 1996 Cell Growth Differ. 7: 961–967.

  • Salomoni P, Perrotti D, Martinez R, Franceschi C and Calabretta B. . 1997 Proc. Natl. Acad. Sci. USA 94: 3296–3301.

  • Taylor D, Badiani P and Weston K. . 1996 Genes Dev. 10: 2732–2744.

  • Thompson M, Rosenthal M, Ellis S, Friend A, Zorbas M, Whitehead R and Ramsay R. . 1998 Cancer Res. 58: 5168–5175.

  • Thompson MA and Ramsay RG. . 1995 Bioessays 17: 341–350.

  • Todokoro K, Watson RJ, Higo H, Amanuma H, Kuramochi S, Yanagisawa H and Ikawa Y. . 1988 Proc. Natl. Acad. Sci. USA 85: 8900–8904.

  • Torelli G, Venturelli D, Colo A, Zanni C, Selleri L, Moretti L, Calabretta B and Torelli U. . 1987 Cancer Res. 47: 5266–5269.

  • Veis DJ, Sentman CL, Bach EA and Korsmeyer SJ. . 1993 J. Immunol. 151: 2546–2554.

  • Wong MH, Hermiston ML, Syder AJ and Gordon JI. . 1996 Proc. Natl. Acad. Sci. USA 93: 9588–9593.

  • Wong MH, Rubinfeld B and Gordon JI. . 1998 J. Cell Biol. 141: 765–777.

  • Wu Q, Chen M, Buchwald M and Phillips RA. . 1995 Nucleic Acids Res. 23: 5087–5088.

  • Yanagisawa H, Nagasawa T, Kuramochi S, Abe T, Ikawa Y and Todokoro K. . 1991 Biochim. Biophys. Acta 1088: 380–384.

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Acknowledgements

We thank Lynne Trute for performing the β-catenin immunohistochemistry, Dr Andreas Strasser for reagents and Michele Cook and Jeon Cha for technical assistance. We also thank Drs Anne Thompson, Maree Overall and Grant McArthur for critical reading of the manuscript and David Bowtell and Joe Sambrook for instructive comments. This work was supported by a National Health and Medical Research Council Research Fellowship and the Anti-Cancer Council of Victoria, Australia.

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  1. Peter MacCallum Cancer Institute, Melbourne, 8006, Australia

    Michelle Zorbas, Catherine Sicurella, Ivan Bertoncello, Deon Venter, Sarah Ellis & Robert G Ramsay

  2. Division of Pulmonary Biology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, 45229-3039, Ohio, OH, USA

    Michael L Mucenski

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  1. Michelle Zorbas
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Zorbas, M., Sicurella, C., Bertoncello, I. et al. c-Myb is critical for murine colon development. Oncogene 18, 5821–5830 (1999). https://doi.org/10.1038/sj.onc.1202971

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