Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

A novel role for IRF-1 as a suppressor of apoptosis

Oncogene volume 19, pages 6386–6391 (2000)Cite this article

Abstract

The tumour suppressor IRF-1 is a transcription factor involved in the induction of apoptosis in several in vitro systems. Post-lactational involution of the mammary gland is characterized by extensive apoptosis of the epithelial cells. We have previously shown that signal transducer and activator of transcription (Stat) 3 drives apoptosis and involution in the mouse mammary gland. Since one of the downstream targets of the Stat signalling pathway is IRF-1, we have used IRF-1 knockout mice to address the potential role of this transcription factor in involution. Surprisingly, in the absence of IRF-1 significantly higher numbers of apoptotic cells were found in involuting glands at 48 h compared to control glands. In addition, the alveolar structure in IRF-1 null mammary glands had collapsed whereas in control glands the alveoli remained intact and distended. However, by 72 h control and null glands were morphologically similar suggesting that IRF-1 suppresses apoptosis only during the early, reversible, stage of involution. This suggests a survival role for IRF-1 in mammary epithelia and demonstrates a novel role for IRF-1 in vivo – suppression of premature epithelial apoptosis during mammary gland involution.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 4
Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Chapman RS, Lourenco PC, Tonner E, Elint DJ, Selbert S, Takeda K, Akira S, Clarke AR and Watson CJ. . 1999 Genes Dev. 13: 2604–2616.

  • Heermeier K, Benedict M, Li ML, Furth P, Nunez G and Henninghausen L. . 1996 Mech. Dev. 56: 197–207.

  • Horiuchi M, Yamada T, Hayashida W and Dzau VJ. . 1997 J. Biol. Chem. 272: 11952–11958.

  • Hossenlopp P, Seurin D, Segoviaquinson B, Hardouin S and Binoux M. . 1986 Analyt. Biochem. 154: 138–143.

  • Jager R, Herzer U, Schenkel J and Weiher H. . 1997 Oncogene 15: 1787–1795.

  • Jerry DJ, Kuperwasser C, Downing SR, Pinkas J, He C, Dickinson E, Marconi S and Naber SP. . 1998 Oncogene 17: 2305–2312.

  • Kirchhoff S and Hauser H. . 1999 Oncogene 18: 3725–3736.

  • Kumar A, Commane M, Flickinger TW, Horvath CM and Stark GR. . 1997 Science 278: 1630–1632.

  • Li ML, Hu JD, Heermeier K, Hennighausen L and Furth PA. . 1996 Cell Growth Differ. 7: 13–20.

  • Li ML, Liu XW, Robinson G, BarPeled U, Wagner KU, Young WS, Hennighausen L and Furth PA. . 1997 Proc. Natl. Acad. Sci. USA 94: 3425–3430.

  • Liu XW, Robinson GW and Hennighausen L. . 1996 Mol. Endocrinol. 10: 1496–1506.

  • Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, Dano K and Werb Z. . 1996 Development 122: 181–193.

  • Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kundig TM, Amakawa R, Kishihara K, Wakeham A, Potter J, Furlonger CL, Narendran A, Suzuki H, Ohashi PS, Paige CJ, Taniguchi T and Mak TW. . 1993 Cell 75: 83–97.

  • Meraro D, Hashmueli S, Koren B, Azriel A, Oumard A, Kirchhoff S, Hauser H, Nagulapalli S, Atchison ML and Levi BZ. . 1999 J. Immunol. 163: 6468–6478.

  • Nguyen H, Lin RT and Hiscott J. . 1997 Oncogene 15: 1425–1435.

  • Nozawa H, Oda E, Nakao K, Ishihara M, Ueda S, Yokochi T, Ogasawara K, Nakatsuru Y, Shimizu S, Ohira Y, Hioki K, Aizawa S, Ishikawa T, Katsuki M, Muto T, Taniguchi T and Tanaka N. . 1999 Genes Dev. 13: 1240–1245.

  • Ogasawara K, Hida S, Azimi N, Tagaya Y, Sato T, YokochiFukuda T, Waldmann TA, Taniguchi T and Taki S. . 1998 Nature 391: 700–703.

  • Philp JAC, Burdon TG and Watson CJ. . 1996 FEBS Lett. 396: 77–80.

  • Strange R, Li F, Saurer S, Burkhardt A and Friis RR. . 1992 Development 115: 49–58.

  • Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S and Taniguchi T. . 1995 Nature 376: 596–599.

  • Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW and Taniguchi T. . 1994 Cell 77: 829–839.

  • Taniguchi T, Lamphier MS and Tanaka N. . 1997 Biochim. Biophys. Acta 1333: M9–M17.

  • Tonner E, Barber MC, Travers MT, Logan A and Flint DJ. . 1997 Endocrinology 138: 5101–5107.

  • Walker NI, Bennett RE and Kerr JFR. . 1989 Am. J. Anat. 185: 19–32.

  • Yuan JP, Wegenka UM, Lutticken C, Buschmann J, Decker T, Schindler C, Heinrich PC and Horn F. . 1994 Mol. Cell. Biol. 14: 1657–1668.

Download references

Acknowledgements

This work was supported by an AICR grant. AR Clarke is a Royal Society University Research Fellow and CJ Watson is funded by the Cancer Research Campaign.

Author information

Authors and Affiliations

  1. Department of Pathology, Cancer Research Campaign (CRC) Laboratories, University of Edinburgh, Medical School, Edinburgh, EH8 9AG, UK

    Rachel S Chapman, Eleanor K Duff & Paula C Lourenco

  2. Hannah Research Institute, Ayr, Scotland, KA6 5HL, UK

    Elizabeth Tonner & David J Flint

  3. School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK

    Alan R Clarke

  4. Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK

    Christine J Watson

Authors
  1. Rachel S Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eleanor K Duff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paula C Lourenco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth Tonner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David J Flint
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alan R Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christine J Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chapman, R., Duff, E., Lourenco, P. et al. A novel role for IRF-1 as a suppressor of apoptosis. Oncogene 19, 6386–6391 (2000). https://doi.org/10.1038/sj.onc.1204016

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204016

Keywords

This article is cited by

Search

Advanced search

Quick links