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.

  • Original Paper
  • Published:

Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines

Oncogene volume 19, pages 223–231 (2000)Cite this article

Abstract

Ectopic expression of the intracellular domain of NOTCH-4/INT-3 leads to tumorigenesis in the mouse mammary gland. This results from a gain-of-function mutation. To evaluate gain-of-function NOTCH-4/INT-3 activity in human cancers we have surveyed human breast, lung, and colon carcinoma tissue culture cell lines for evidence of increased NOTCH-4/INT-3 RNA expression. High levels of a 1.8 Kb NOTCH-4/INT-3 RNA species are detected in normal human testis but not in other tissues where a 6.5 Kb species is prevalent. Transformed human cancer cell lines express the 1.8 Kb NOTCH-4/INT-3 RNA species. We show that this RNA species encodes a truncated form of the NOTCH-4/INT-3 intracellular domain (ICD). This novel NOTCH-4/INT-3 protein includes the CDC10 repeats and amino acid residues C-terminal to them, but is missing the CBF-1 binding region of the NOTCH-4/INT-3 ICD. This suggests that it has a different mode of action. Furthermore, we show that a transgene which expresses the 1.8 Kb NOTCH-4/INT-3 RNA species in the `normal' human mammary epithelial cell line MCF-10A enables these cells to grow in soft agar.

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 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Artavanis-Tsakonas S, Rand MD and Lake RJ . 1999 Science 284: 770–776.

  • Aspenstrom P and Olson MF . 1995 Methods Enzymol 256: 228–241.

  • Aster J, Pear W, Hasserjian R, Erba H, Davi F, Luo B, Scott M, Baltimore D and Sklar J . 1994 Cold Spring Harbor Symp Quant Biol 59: 125–136.

  • Bailey AM and Posakony JW . 1995 Genes Dev 9: 2609–2622.

  • Blaumueller CM, Qi H, Zagouras P and Artavanis-Tsakonas S . 1997 Cell 90: 281–291.

  • Capobianco AJ, Zagouras P, Blaumueller CM, Artavanis-Tsakonas S and Bishop JM . 1997 Mol Cell Biol 17: 6265–6273.

  • De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A and Kopan R . 1999 Nature 398: 518–522.

  • Ellison LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD and Sklar J . 1991 66: 649–661.

  • Gallahan D and Callahan R . 1997 Oncogene 14: 1883–1890.

  • Gallahan D, Jhappan C, Robinson G, Hennighausen L, Sharp R, Kordon E, Callahan R, Merlino G and Smith GH . 1996 Cancer Res 56: 1775–1785.

  • Girard L, Hanna Z, Beaulieu N, Hoemann CD, Simard C, Kozak CA and Jolicoeur P . 1996 Genes Dev 10: 1930–1944.

  • Hardy J and Israel A . 1999 Nature 398: 466–467.

  • Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R and Israel A . 1995 Nature 377: 355–358.

  • Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G and Callahan R . 1992 Genes Dev 6: 345–355.

  • Jolicoeur P, Bouchard L, Guimond A, Ste-Marie M, Hanna Z and Dievart A . 1998 Biochem Soc Symp 63: 159–165.

  • Kopan R, Nye JS and Weintraub H . 1994 Development 120: 2385–2396.

  • Kopan R, Schroeter EH, Weintraub H and Nye JS . 1996 Proc Natl Acad Sci USA 93: 1683–1688.

  • Kozak M . 1989 J Cell Biol 108: 229–241.

  • Lecourtois M and Schweisguth F . 1995 Genes Dev 9: 2598–2608.

  • Li L, Huang GM, Banta AB, Deng Y, Smith T, Dong P, Friedman C, Chen L, Trask BJ, Spies T, Rowen L and Hood L . 1998 Genomics 51: 45–58.

  • Logeat F, Bessia C, Brou C, LeBail O, Jarriault S, Seidah NG and Israel A . 1998 Proc Natl Acad Sci USA 95: 8108–8112.

  • Matsuno K, Go J, Sun X, Eastman DS and Artavanis-Tsakonas S . 1997 Development 124: 4265–4273.

  • Needleman SB and Wunsch CD . 1970 J Mol Biol 48: 443–453.

  • Robbins J, Blondel BJ, Gallahan D and Callahan R . 1992 J Virol 66: 2594–2599.

  • Rohn JL, Lauring AS, Linenberger ML and Overbaugh J . 1996 J Virol 70: 8071–8080.

  • Sarkar NH, Haga S, Lehner AF, Zhao W, Imai S and Moriwaki K . 1994 Virology 203: 52–62.

  • Sasai Y, Kageyama R, Tagawa Y, Shigemoto R and Nakanishi S . 1992 Genes Dev 6: 2620–2634.

  • Shawber C, Nofziger D, Hsieh JJ-D, Lindsell C, Bogler O, Hayward D and Weinmaster G . 1996 Development 122: 3765–3773.

  • Smith GH, Gallahan D, Diella F, Jhappan C, Merlino G and Callahan R . 1995 Cell Growth Differ 6: 563–577.

  • Smith TF and Waterman MS . 1981 Adv App Math 2: 482–489.

  • Smithies O, Engels WR, Devereux JR and Slightom JLaSS . 1981 Cell 26: 345–353.

  • Staden R . 1980 NAR 8: 3673–3694.

  • Struhl G and Greenwald I . 1999 Nature 398: 522–525.

  • Uyttendaele H, Marazzi G, Wu G, Yan Q, Sassoon D and Kitajewski J . 1996 Development 122: 2251–2259.

  • Uyttendaele H, Soriano JV, Montesano R and Kitajewski J . 1998 Dev Biol 196: 204–217.

  • Valverius EM, Ciardiello F, Heldin NE, Blondel B, Merlo G, Smith G, Stampfer MR, Lippman ME, Dickson RB and Salomon DS . 1990 J Cell Physiol 145: 207–216.

  • Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT and Selkoe DJ . 1999 Nature 398: 513–517.

  • Ye Y, Lukinova N and Fortini ME . 1999 Nature 398: 525–529.

Download references

Acknowledgements

We thank Sharon Bargo for her excellent technical assistance, Dr Daniel Gallahan for helpful discussions, and Dr Gilbert H Smith for critically reading the manuscript.

Author information

Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, 20892, Maryland, MD, USA

    Akira Imatani & Robert Callahan

Authors
  1. Akira Imatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Callahan
    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

Imatani, A., Callahan, R. Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. Oncogene 19, 223–231 (2000). https://doi.org/10.1038/sj.onc.1203295

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203295

Keywords

This article is cited by

Search

Advanced search

Quick links