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Bcl-w is an important determinant of damage-induced apoptosis in epithelia of small and large intestine

Oncogene volume 19, pages 3955–3959 (2000)Cite this article

Abstract

The potential role of the bcl-2 relative bcl-w as a physiological regulator of apoptosis in intestinal epithelia has been investigated. Immunoblots for bcl-w with new monoclonal antibodies revealed that it was expressed in the small intestine and colon, among other murine tissues, as well as in six human tumour cell lines of epithelial origin, including two colon carcinoma lines. To assess whether bcl-w regulates either spontaneous or damage-induced apoptosis in the small intestine or colon, apoptosis in intestinal crypts of bcl-w −/− and wild-type mice was quantified microscopically on a cell positional basis. Spontaneous apoptosis within crypt epithelia was not significantly increased by loss ofbcl-w, in either the small intestine or midcolon. However, after treatment with the cytotoxic drug 5-fluorouracil or with γ-radiation, the bcl-w-null animals exhibited substantially more apoptosis than their wild-type counterparts in both tissues. The greatest enhancement of apoptosis attributable to the absence of bcl-w (up to sixfold) occurred in the small intestine. Hence, bcl-w is an important determinant of damage-induced apoptosis in intestinal epithelia, and unlike bcl-2, which regulates only colonic apoptosis, plays a major role in small intestinal epithelium.

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Abbreviations

5-FU:

5-fluorouracil

References

  • Adams JM and Cory S. . 1998 Science 281: 1322–1326.

  • Dive C and Hickman JA. . 1991 Br. J. Cancer 64: 192–196.

  • Gibson L, Holmgreen SP, Huang DCS, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM and Cory S. . 1996 Oncogene 13: 665–675.

  • Manne U, Myers RB, Moron C, Poczatek RB, Dillard S, Weiss H, Brown D, Srivastava S and Grizzle WE. . 1997 Int. J. Cancer 74: 346–358.

  • Merritt AJ, Jones LS and Potten CS. . 1996 Techniques in Apoptosis. Cotter and Martin (eds), Portland Press Ltd., London pp. 269–300.

  • Merritt AJ, Potten CS, Kemp CJ, Hickman JA, Ballmain A, Lane DP and Hall PA. . 1994 Cancer Res. 54: 614–617.

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

  • Potten CS. . 1977 Nature 269: 518–521.

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

  • Potten CS and Grant HK. . 1998 Br. J. Cancer 78: 993–1003.

  • Potten CS, Owen G and Roberts SA. . 1990 Int. J. Radiat. Biol. 57: 185–199.

  • Print CG, Loveland KL, Gibson L, Meehan T, Stylianou A, Wreford N, DeKretser D, Metcalf D, Kontgen F, Adams JM and Cory S. . 1998 Proc. Natl. Acad. Sci. USA 95: 12424–12431.

  • Pritchard DM, Potten CS and Hickman JA. . 1998 Cancer Res. 58: 5453–5465.

  • Pritchard DM, Potten CS, Korsmeyer SJ, Roberts S and Hickman JA. . 1999 Oncogene 18: 7287–7293.

  • Pritchard DM, Watson AJ, Potten CS, Jackman AL and Hickman JA. . 1997 Proc. Natl. Acad. Sci. USA. 94: 1795–1799.

  • Reed JC. . 1999 Apoptosis and Cancer Chemotherapy, Hickman JA and Dive C. (eds). Humana Press, Totowa, NJ pp. 99–116.

  • Ross AI, Waymire KG, Moss JE, Parlow AF, Skinner MK, Russell LD and MacGregor G. . 1998 Nature Genetics 18: 251–256.

  • Veis DJ, Sorenson CM, Shutter JR and Korsmeyer SJ. . 1993 Cell 75: 229–239.

  • Watson AJM, Merritt AJ, Jones LS, Askew JN, Anderson E, Becciolini A, Balzi M, Potten CS and Hickman JA. . 1996 Br. J. Cancer 73: 889–895.

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Acknowledgements

We thank Susanna Novakovi, Leonie Cullen and Evette Shomali for technical assistance and for research support, the Medical Research Council (UK), the Cancer Research Campaign (UK), AMRAD Biotech, the National Health and Medical Research Council (Australia), the US National Cancer Institute (CA 43540 and CA80188) and the Dr Josef Steiner Cancer Foundation.

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Author notes

  1. C Print

    Present address: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK

  2. J A Hickman

    Present address: Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France

Authors and Affiliations

  1. CRC Department of Epithelial Biology, Paterson Institute, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 9BX, UK

    D M Pritchard & C S Potten

  2. CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, Stopford Building (G38), University of Manchester, Manchester, M13 9PT, UK

    D M Pritchard & J A Hickman

  3. The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, 3050, Australia

    C Print, L O'Reilly & J M Adams

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Pritchard, D., Print, C., O'Reilly, L. et al. Bcl-w is an important determinant of damage-induced apoptosis in epithelia of small and large intestine. Oncogene 19, 3955–3959 (2000). https://doi.org/10.1038/sj.onc.1203729

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