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  • Poster Presentation
  • Open Access

Insulin-like growth factor signalling in oestrogen nonresponsive breast cancer cells

  • 1,
  • 1 and
  • 1
Breast Cancer Research20068 (Suppl 2) :P16

https://doi.org/10.1186/bcr1571

  • Published:

Keywords

  • Endocrine Resistant Breast Cancer
  • Endocrine Resistant Breast
  • Nonresponsive Breast Cancer

Background

Insulin-like growth factors (IGFs) regulate normal growth and development. In breast cancer, they stimulate cell proliferation, cell migration and inhibit apoptosis. The IGF signal transduction pathway is, therefore, a potential therapeutic target in the treatment of breast cancer [1, 2]. Inhibitors of the IGF pathway may be effective in the treatment of breast cancer with de novo or acquired endocrine resistance. We have studied IGF signalling in oestrogen nonresponsive MDA-MB-231, HBL-100 and BT-20 breast cancer cell lines as models of endocrine resistant breast cancer. Oestrogen responsive MCF-7 cells were also studied.

Results

Components of the IGF signalling pathway, type I IGF Receptor (IGF1R), IRS-1, IRS-2, and the three Shc isoforms, were expressed at varying levels, demonstrating a range of phenotypes in the breast cancer cells. IRS-1 is expressed in a truncated form in the BT-20 cells as an antibody to the C-terminus is unable to detect the protein.

IGF-1 activated IGF1R, IRS-1, MAP kinase and Akt in the MCF-7, MDA-MB-231 and HBL-100 cell lines. IGF-1 stimulated phosphorylation of IGF1R in BT-20 cells but did not alter the level of activation of IRS-1, MAP kinase or Akt. The MEK1/2 inhibitor (PD 98059) and the PI-3 kinase inhibitor (LY 294002) decreased the level of phosphorylation of MAP kinase and Akt in BT-20 cells. A phosphospecific antibody to tyrosine 896, the Grb2 SH2 binding site, shows that IRS-1 is constitutively phosphorylated in BT-20 cells.

IGF-1 inhibited staurosporine-induced apoptosis in MCF-7, MDA-MB-231 and HBL-100 cells but not in BT-20 cells. Inhibition of the IGF signalling pathways with PD 98059 and LY 294002 sensitise MDA-MB-231 cells to staurosporine-induced apoptosis. IGF-1 stimulated growth in MCF-7 and MDA-MB-231 cells but not in BT-20 cells.

Conclusion

Expression and activation of IGF signalling proteins vary among the oestrogen nonresponsive cells. These differences will affect the response of breast cancer cells to IGF targeted therapy. BT-20 cells provide a useful model for constitutive IRS-1 phosphorylation which is reported to occur in breast tumours [3].

Declarations

Acknowledgements

This project was funded by Breast Cancer Campaign.

Authors’ Affiliations

(1)
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

References

  1. Molloy CA, May FEB, Westley BR: Insulin receptor substrate-1 expression is regulated by estrogen in the MCF-7 human breast cancer cell line. J Biol Chem. 2000, 275: 12565-12571. 10.1074/jbc.275.17.12565.View ArticlePubMedGoogle Scholar
  2. Garber K: IGF-1: old growth factor shines as new drug target. J Natl Cancer Inst. 2005, 97: 790-792.View ArticlePubMedGoogle Scholar
  3. Chang Q, Li Y, White MF, Fletcher JA, Xiao S: Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumours: therapeutic implications. Cancer Res. 2002, 62: 6035-6038.PubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2006

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