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:

Regulation of cyclin expression and cell cycle progression in breast epithelial cells by the helix–loop–helix protein Id1

Oncogene volume 24, pages 381–389 (2005)Cite this article

Abstract

The helix–loop–helix protein Id1 has been implicated in regulating mammary epithelial cell proliferation and differentiation but the underlying molecular mechanisms are not well characterized. Under low serum conditions, ectopic expression of Id1, but not Id2, allowed continued proliferation of immortalized mammary epithelial cells and breast cancer cells. Conversely, downregulation of Id1 impaired proliferation. The effects of short interfering RNA (siRNA)-mediated downregulation of Id1 were the same as those following downregulation of c-Myc: decreased expression of cyclins D1 and E, reduced phosphorylation of pRb at Ser780 (a site targeted by cyclin D1–Cdk4) and reduced cyclin E–Cdk2 activity. Decreased cyclin D1 expression was an early response to Id1 antisense oligonucleotide treatment. Inhibition of c-Myc function by siRNA, antisense oligonucleotides or a dominant repressor resulted in downregulation of Id1, while ectopic expression of c-Myc resulted in rapid induction of Id1, suggesting that Id1 may be downstream of c-Myc. These data indicate that in mammary epithelial cells, Id1 has cell cycle regulatory functions that are similar to those of c-Myc, and suggest that cyclin D1 may be involved in Id1 regulation of cell cycle progression.

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 6
Figure 3
Figure 4
Figure 5
Figure 7

Similar content being viewed by others

References

  • Alani RM, Hasskarl J, Grace M, Hernandez M-C, Israel MA and Munger K . (1999). Proc. Natl. Acad. Sci. USA, 96, 9637–9641.

  • Alani RM, Young AZ and Shifflett CB . (2001). Proc. Natl. Acad. Sci. USA, 98, 7812–7816.

  • Amati B, Alevizopoulos K and Vlach J . (1998). Front. Biosci., 3, d250–d268.

  • Baldin V, Lukas J, Marcote MJ, Pagano M and Draetta G . (1993). Genes Dev., 7, 812–821.

  • Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN and Weintraub H . (1990). Science, 250, 1149–1151.

  • Caplen NJ, Parrish S, Imani F, Fire A and Morgan RA . (2001). Proc. Natl. Acad. Sci. USA, 98, 9742–9747.

  • Carroll JS, Prall OWJ, Musgrove EA and Sutherland RL . (2000). J. Biol. Chem., 275, 38221–38229.

  • Carroll JS, Swarbrick A, Musgrove EA and Sutherland RL . (2002). Cancer Res., 62, 3126–3131.

  • Desprez PY, Hara E, Bissell MJ and Campisi J . (1995). Mol. Cell. Biol., 15, 3398–3404.

  • Desprez PY, Lin CQ, Thomasset N, Sympson CJ, Bissell MJ and Campisi J . (1998). Mol. Cell. Biol., 18, 4577–4588.

  • Desprez PY, Sumida T and Coppe JP . (2003). J. Mammary Gland Biol. Neoplasia, 8, 225–239.

  • Dubik D, Dembinski TC and Shiu RPC . (1987). Cancer Res., 47, 6517–6521.

  • Elbashir SM, Harborth J, Weber K and Tuschl T . (2002). Methods, 26, 199–213.

  • Grandori C, Mac J, Siebelt F, Ayer DE and Eisenmann RN . (1996). EMBO J., 15, 4344–4357.

  • Guan XY, Xu J, Anzick SL, Zhang H, Trent JM and Meltzer PS . (1996). Cancer Res., 56, 3446–3450.

  • Halevy O, Novitch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ, Beach D and Lassar AB . (1995). Science, 267, 1018–1021.

  • Hara E, Yamaguchi T, Nojima H, Ide T, Campisi J, Okayama H and Oda K . (1994). J. Biol. Chem., 269, 2139–2145.

  • Holmes ML, Haley JD, Cerruti L, Zhou WL, Zogos H, Smith DE, Cunningham JM and Jane SM . (1999). Mol. Cell. Biol., 19, 4182–4190.

  • Iavarone A, Garg P, Lasorella A, Hsu J and Israel M . (1994). Genes Dev., 8, 1270–1284.

  • Itahana Y, Singh J, Sumida T, Coppe JP, Parrinello S, Bennington JL and Desprez PY . (2003). Cancer Res., 63, 7098–7105.

  • Kitagawa M, Higashi H, Jung H-K, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J-Y, Segawa K, Yoshida E, Nishimura S and Taya Y . (1996). EMBO J., 15, 7060–7069.

  • Kolligs FT, Nieman MT, Winer I, Hu G, Van Mater D, Feng Y, Smith IM, Wu R, Zhai Y, Cho KR and Fearon ER . (2002). Cancer Cell, 1, 145–155.

  • Lin CQ, Singh J, Murata K, Itahana Y, Parrinello S, Liang SH, Gillett CE, Campisi J and Desprez PY . (2000). Cancer Res., 60, 1332–1340.

  • Massari ME and Murre C . (2000). Mol. Cell. Biol., 20, 429–440.

  • Miyoshi K, Meyer B, Gruss P, Cui Y, Renou J-P, Morgan FV, Smith GH, Reichenstein M, Shani M, Hennighausen L and Robinson GW . (2002). Mol. Endocrinol., 16, 2892–2901.

  • Mori S, Nishikawa S-I and Yokota Y . (2000). EMBO J., 19, 5772–5781.

  • Musgrove EA, Hunter LK, Lee CS, Swarbrick A, Hui R and Sutherland RL . (2001). J. Biol. Chem., 276, 47675–47683.

  • Musgrove EA, Lilischkis R, Cornish AL, Lee CS, Setlur V, Seshadri R and Sutherland RL . (1995). Int. J. Cancer, 63, 584–591.

  • Norton J . (2000). J. Cell Sci., 113, 3897–3905.

  • Ohtani N, Zebedee Z, Huot TJG, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G and Hara E . (2001). Nature, 409, 1067–1070.

  • Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM and Pagano M . (1995). Mol. Cell. Biol., 15, 2612–2624.

  • Oster SK, Ho CSW, Soucie EL and Penn LZ . (2002). Adv. Cancer Res., 84, 81–154.

  • Parrinello S, Lin CQ, Murata K, Itahana Y, Singh J, Krtolica A, Campisi J and Desprez PY . (2001). J. Biol. Chem., 276, 39213–39219.

  • Peverali F, Ramqvist T, Saffrich R, Pepperkok R, Barone M and Philipson L . (1994). EMBO J., 13, 4291–4301.

  • Prabhu S, Ignatova A, Park S and Sun X . (1997). Mol. Cell. Biol., 17, 5888–5896.

  • Prall OWJ, Rogan EM, Musgrove EA, Watts CK and Sutherland RL . (1998). Mol. Cell. Biol., 18, 4499–4508.

  • Prall OWJ, Sarcevic B, Musgrove EA, Watts CKW and Sutherland RL . (1997). J. Biol. Chem., 272, 10882–10894.

  • Schoppmann SF, Schindl M, Bayer G, Aumayr K, Dienes J, Horvat R, Rudas M, Gnant M, Jakesz R and Birner P . (2003). Int. J. Cancer, 104, 677–682.

  • Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, Skoultchi AI and DePinho RA . (1995). Cell, 80, 777–786.

  • Sikder HA, Devlin MK, Dunlap S, Ryu B and Alani RM . (2003). Cancer Cell, 3, 525–530.

  • Sutherland RL, Prall OW, Watts CK and Musgrove EA . (1998). J. Mammary Gland Biol. Neoplasia, 3, 63–72.

  • Swarbrick A, Lee CS, Sutherland RL and Musgrove EA . (2000). Mol. Cell. Biol., 20, 2581–2591.

  • Tanner MM, Tirkkonen M, Kallioniemi A, Isola J, Kuukasjarvi T, Collins C, Kowbel D, Guan XY, Trent J, Gray JW, Meltzer P and Kallioniemi OP . (1996). Cancer Res., 56, 3441–3445.

  • Tikhonenko AT, Black DJ and Linial ML . (1996). J. Biol. Chem., 271, 30741–30747.

  • Tournay O and Benezra R . (1996). Mol. Cell. Biol., 16, 2418–2430.

  • Volpert OV, Pilli R, Sikder HA, Nelius T, Zaichuk T, Morris C, Shiflett CB, Devlin MK, Conant K and Alani RM . (2002). Cancer Cell, 2, 473–483.

  • von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, Hydbring P, Weidung I, Nakayama K, Nakayama KI, Soderberg O, Kerppola TK and Larsson LG . (2003). Mol Cell, 11, 1189–1200.

  • Wang J, Xie LY, Allan S, Beach D and Hannon GJ . (1998). Genes Dev., 12, 1769–1774.

  • Watson PH, Pon RT and Shiu RPC . (1991). Cancer Res., 51, 3996–4000.

  • Wingender E, Chen X, Fricke E, Geffers R, Hehl R, Liebich I, Krull M, Matys V, Michael H, Ohnhauser R, Pruss M, Schacherer F, Thiele S and Urbach S . (2001). Nucleic Acids Res., 29, 281–283.

  • Yates PR, Atherton GT, Deed RW, Norton JD and Sharrocks AD . (1999). EMBO J., 18, 968–976.

Download references

Acknowledgements

We thank the following colleagues: Joseph Webster (Centenary Institute of Cancer Medicine and Cell Biology, Sydney) and Dr Rebecca Newton for flow cytometric cell sorting; Dr Pierre Yves Desprez (Geraldine Brush Cancer Research Institute, San Francisco) and Dr Jason Carroll for helpful discussions, reagents and advice; and Dr Rania Kairouz and Dr Sophie Doisneau-Sixou for their contributions to some experiments. This research was supported by the National Health and Medical Research Council of Australia, The Cancer Council NSW, The Cure Cancer Australia Foundation and The Association of International Cancer Research. AS was a recipient of an Australian Postgraduate Award and a Fatemeh Moradzadeh Fellowship. CEC is a recipient of an Australian Postgraduate Award, the LH Ainsworth Scholarship for Cancer Research and the Beth Yarrow Scholarship in Medical Science.

Author information

Author notes

  1. Alexander Swarbrick

    Present address: GW Hooper Foundation, University of California, Box 0552, HSW 1531, 513 Parnassus, San Francisco, CA, 94143-0552, USA

Authors and Affiliations

  1. Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia

    Alexander Swarbrick, Mia C Åkerfeldt, Christine S L Lee, C Marcelo Sergio, C Elizabeth Caldon, Lisa-Jane K Hunter, Robert L Sutherland & Elizabeth A Musgrove

Authors
  1. Alexander Swarbrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mia C Åkerfeldt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine S L Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Marcelo Sergio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Elizabeth Caldon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lisa-Jane K Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert L Sutherland
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elizabeth A Musgrove
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth A Musgrove.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Swarbrick, A., Åkerfeldt, M., Lee, C. et al. Regulation of cyclin expression and cell cycle progression in breast epithelial cells by the helix–loop–helix protein Id1. Oncogene 24, 381–389 (2005). https://doi.org/10.1038/sj.onc.1208188

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208188

Keywords

This article is cited by

Search

Advanced search

Quick links