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.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 29 January 1999

Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line

  • J P Parisot1,
  • X F Hu1,
  • M DeLuise2 &
  • …
  • J R Zalcberg1 

British Journal of Cancer volume 79, pages 693–700 (1999)Cite this article

  • 1379 Accesses

  • 78 Citations

  • Metrics details

This article has been updated

Abstract

The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5–21) and tamoxifen-resistant (MCF 7/5–23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E2or IGF-1 or a combination of both agents. Growth of both MCF 7/5–21 and 7/5–23 cells was stimulated (245% and 350%, respectively) by E2. However, only the growth of MCF 7/5–23 cells was stimulated (266%) by IGF-1. A combination of E2and IGF-1 significantly enhanced MCF 7/5–21 and 7/5–23 cell growth (581% and 695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by 125I-IGF-1 binding and Northern analyses) in only MCF 7/5–23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5–23 cells was significantly inhibited by the IGF-1R monoclonal antibody, αIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5–23 cells. These experiments indicate that E2may sensitize tamoxifen-resistant MCF 7/5–23 cells to the growth stimulatory actions of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance.

Similar content being viewed by others

Insulin-like growth factor binding protein-3 induces senescence by inhibiting telomerase activity in MCF-7 breast cancer cells

Article Open access 30 May 2023

Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression

Article Open access 03 October 2024

Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2

Article Open access 19 August 2023

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Arteaga, C. L. & Osborne, C. K. (1989). Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res, 49, 6237–6241.

    CAS  PubMed  Google Scholar 

  • Baserga, R., Hongo, A., Rubini, M., Prisco, M. & Valentinis, B. (1997). The IGF-1 receptor in cell growth, transformation and apoptosis. Biochim Biophys Acta, 1332, F105–F126.

    CAS  PubMed  Google Scholar 

  • Berthois, Y., Katzenellenbogen, J. & Katzenellenbogen, B. (1986). Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci USA, 83, 2496–2500.

    Article  CAS  Google Scholar 

  • Chomczynski, P. & Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem, 162, 156–159.

    Article  CAS  Google Scholar 

  • Clarke, R., Howell, A. & Anderson, E. (1997). Type I insulin-like growth factor receptor gene expression in normal human breast tissue treated with oestrogen and progesterone. Br J Cancer, 75, 251–257.

    Article  CAS  Google Scholar 

  • Darbre, P., Yates, J., Curtis, S. & King, R. (1983). Effect of estradiol on human breast cancer cells in culture. Cancer Res, 43, 349–354.

    CAS  PubMed  Google Scholar 

  • Decupis, A., Noonan, D., Pirani, P., Ferrera, A., Clerico, L. & Favoni, R. E. (1995). Comparison between novel steroid-like and conventional nonsteroidal antioestrogens in inhibiting oestradiol- and IGF-1-induced proliferation of human breast cancer-derived cells. Br J Pharmacol, 116, 2391–2400.

    Article  CAS  Google Scholar 

  • Dickson, R. B., Johnson, M. D., el Ashry, D., Shi, Y. E., Bano, M., Zugmaier, G., Ziff, B., Lippman, M. E. & Chrysogelos, S. (1993). Breast cancer: influence of endocrine hormones, growth factors and genetic alterations. Adv Exp Med Biol, 330, 119–141.

    Article  CAS  Google Scholar 

  • Dunn, S., Hardman, R., Kari, F. & Barrett, J. (1997). Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. Cancer Res, 57, 2687–2693.

    CAS  PubMed  Google Scholar 

  • Encarnacion, C. A. & Fuqua, S. A. (1994). Oestrogen receptor variants in breast cancer. Cancer Treat Res, 71, 97–109.

    Article  CAS  Google Scholar 

  • Freiss, G., Rochefort, H. & Vignon, F. (1990). Mechanisms of 4-hydroxytamoxifen anti-growth factor activity in breast cancer cells: alterations of growth factor receptor binding sites and tyrosine kinase activity. Biochem Biophys Res Commun, 173, 919–926.

    Article  CAS  Google Scholar 

  • Hu, X. F., Veroni, M., De Luise, M., Wakeling, A., Sutherland, R., Watts, C. K. & Zalcberg, J. R. (1993). Circumvention of tamoxifen resistance by the pure antioestrogen ICI 182,780. Int J Cancer, 55, 873–876.

    Article  CAS  Google Scholar 

  • Huff, K., Kaufman, D., Gabbay, K. H., Spencer, E. M., Lippman, M. E. & Dickson, R. B. (1986). Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res, 46, 4613–4619.

    CAS  PubMed  Google Scholar 

  • Huynh, H., Nickerson, T., Pollak, M. & Yang, X. F. (1996). Regulation of insulin-like growth factor I receptor expression by the pure antioestrogen ICI 182,780. Clin Cancer Res, 2, 2037–2042.

    CAS  PubMed  Google Scholar 

  • Jones, J. I. & Clemmons, D. R. (1995). Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev, 16, 3–34.

    CAS  PubMed  Google Scholar 

  • Karey, K. & Sirbasku, D. (1988). Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. Cancer Res, 48, 4083–4092.

    CAS  PubMed  Google Scholar 

  • Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., Metzger, D. & Chambon, P. (1995). Activation of the oestrogen receptor through phosphorylation by mitogen-activated protein kinase. Science, 270, 1491–1494.

    Article  CAS  Google Scholar 

  • Katzenellenbogen, B. S. & Norman, M. J. (1990). Multihormonal regulation of the progesterone receptor in MCF-7 human breast cancer cells: interrelationships among insulin/insulin-like growth factor-I, serum, and oestrogen (published erratum appears in Endocrinology 1990; 126: 3217). Endocrinology, 126, 891–898.

    Article  CAS  Google Scholar 

  • Kleinman, D., Karas, M., Roberts, C. J., LeRoith, D., Phillip, M., Segev, Y., Levy, J. & Sharoni, Y. (1995). Modulation of insulin-like growth factor I (IGF-1) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol. Endocrinology, 136, 2531–2537.

    Article  CAS  Google Scholar 

  • Kull-Jr, F. C., Jacobs, S., Su, Y., Svoboda, M., Van Wyk, J. & Cuatrecasas, P. (1983). Monoclonal antibodies to receptors for insulin and somatomedin-C. J Biol Chem, 258, 6561–6566.

    CAS  Google Scholar 

  • Lee, A. V. & Yee, D. (1995). Insulin-like growth factors and breast cancer. Biomed Pharmacother, 49, 415–421.

    Article  CAS  Google Scholar 

  • Lee, A. V., Darbre, P. & King, R. (1994a). Processing of insulin-like growth factor-II (IGF-II) by human breast cancer cells. Mol Cell Endocrinol, 99, 211–220.

    Article  CAS  Google Scholar 

  • Lee, A. V., Toi, M. & Yee, D. (1994b). Tamoxifen resistant MCF 7 cells exhibit increased expression of insulin-like growth factor-II (IGF-II). Breast Cancer Res Treat, 32S, 57

    Google Scholar 

  • Lippman, M. E. (1985). Growth regulation of human breast cancer. Clin Res, 47, 375–382.

    Google Scholar 

  • McCotter, D., Vandenberg, H. W., Boylan, M. & McKibben, B. (1996). Changes in insulin-like growth factor-I receptor expression and binding protein secretion associated with tamoxifen resistance and oestrogen independence in human breast cancer cells in vitro. Cancer Lett, 99, 239–245.

    Article  CAS  Google Scholar 

  • Musgrove, E. A. & Sutherland, R. L. (1993). Acute effects of growth factors on T47D breast cancer cell cycle progression. Eur J Cancer, 29A, 2273–2279.

    Article  CAS  Google Scholar 

  • Newton, C. J., Trapp, T., Pagotto, U., Renner, U., Buric, R. & Stalla, G. K. (1994). The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen. J Mol Endocrinol, 12, 303–312.

    Article  CAS  Google Scholar 

  • Osborne, C., Coronado, E. B., Kitten, L. J., Arteaga, C. L., Fuqua, S. A., Ramasharma, K., Marshall, M. & Li, C. H. (1989). Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-1 receptor. Mol Endocrinol, 3, 1701–1709.

    Article  CAS  Google Scholar 

  • Papa, V., Gliozzo, B., Clark, G. M., McGuire, W. L., Moore, D., Fujitayamaguchi, Y., Vigneri, R., Goldfine, I. D. & Pezzino, V. (1993). Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer. Cancer Res, 53, 3736–3740.

    CAS  PubMed  Google Scholar 

  • Parisot, J. P., Hu, X. F., Sutherland, R., Wakeling, A., Zalcberg, J. & DeLuise, M. (1995). The pure antioestrogen ICI 182,780 binds to a high-affinity site distinct from the oestrogen receptor. Int J Cancer, 62, 480–484.

    Article  CAS  Google Scholar 

  • Pekonen, F., Partanen, S., Makinen, T. & Rutanen, E. (1988). Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res, 48, 1343–1347.

    CAS  PubMed  Google Scholar 

  • Peyrat, J., Bonneterre, J., Hecquet, B., Vennin, P., Louchez, M., Fournier, C., Lefebvre, J. & Demaille, A. (1993). Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur J Cancer, 29A, 492–497.

    Article  CAS  Google Scholar 

  • Quinn, K. A., Treston, A. M., Unsworth, E. J., Miller, M. J., Vos, M., Grimley, C., Battey, J., Mulshine, J. L. & Cuttitta, F. (1996). Insulin-like growth factor expression in human cancer cell lines. J Biol Chem, 271, 11477–11483.

    Article  CAS  Google Scholar 

  • Reddel, R. R., Alexander, I. E., Masfumi, K., Shine, J. & Sutherland, R. (1988). Genetic instability and the development of steroid hormone insensitivity in cultured T47D human breast cancer cells. Cancer Res, 48, 4340–4347.

    CAS  PubMed  Google Scholar 

  • Resnicoff, M., Abraham, D., Yutanawiboonchai, W., Rotman, H. L., Kajstura, J., Rubin, R., Zoltick, P. & Baserga, R. (1995). The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res, 55, 2463–2469.

    CAS  PubMed  Google Scholar 

  • Rohlik, Q., Adams, D., Kull, F. C. Jr & Jacobs, S. (1987). An antibody to the receptor for insulin-like growth factor I inhibits the growth of MCF-7 cells in tissue culture. Biochem Biophys Res Commun, 149, 276–281.

    Article  CAS  Google Scholar 

  • Steele-Perkins, G., Turner, J., Edman, J. C., Hari, J., Pierce, S. B., Stover, C., Rutter, W. J. & Roth, R. A. (1988). Expression and characterization of a functional human insulin-like growth factor I receptor. J Biol Chem, 263, 11486–11492.

    CAS  PubMed  Google Scholar 

  • Stewart, A. J., Johnson, M. D., May, F. E. & Westley, B. (1990). Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the oestrogen-stimulated proliferation of human breast cancer cells. J Biol Chem, 265, 21172–21178.

    CAS  PubMed  Google Scholar 

  • Stewart, A. J., Westley, B. & May, F. (1992). Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen. Br J Cancer, 66, 640–648.

    Article  CAS  Google Scholar 

  • Thorsen, T., Lahooti, H., Rasmussen, M. & Aakvaag, A. (1992). Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-1. J Steroid Biochem Mol Biol, 41, 537–540.

    Article  CAS  Google Scholar 

  • Toi, M., Harris, A. & Bicknell, R. (1993). cDNA transfection followed by the isolation of a MCF-7 breast cell line resistant to tamoxifen in vitro and in vivo. Br J Cancer, 68, 1088–1096.

    Article  CAS  Google Scholar 

  • Ullrich, A., Gray, A., Tam, A., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., Chen, E., et al (1986). Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J, 5, 2503–2512.

    Article  CAS  Google Scholar 

  • van den Berg, H. W., Claffie, D., Boylan, M., McKillen, J., Lynch, M. & McKibben, B. (1996). Expression of receptors for epidermal growth factor and insulin-like growth factor I by ZR-75-1 human breast cancer cell variants is inversely related – the effect of steroid hormones on insulin-like growth factor I receptor expression. Br J Cancer, 73, 477–481.

    Article  CAS  Google Scholar 

  • Werner, H., Woloschak, M., Adamo, M., Shen-Orr, Z., Roberts, C. T. Jr & LeRoith, D. (1989). Developmental regulation of the rat insulin-like growth factor I receptor gene. Proc Natl Acad Sci USA, 86, 7451–7455.

    Article  CAS  Google Scholar 

  • Westley, B. R. & May, F. (1994). Role of insulin-like growth factors in steroid modulated proliferation (Review). J Steroid Biochem Mol Biol, 51, 1–9.

    Article  CAS  Google Scholar 

  • Wiseman, L. R., Johnson, M. D., Wakeling, A. E., Lykkesfeldt, A. E., May, F. E. & Westley, B. R. (1993). Type I IGF receptor and acquired tamoxifen resistance in oestrogen-responsive human breast cancer cells. Eur J Cancer, 29A, 2256–2264.

    Article  CAS  Google Scholar 

  • Yee, D., Cullen, K. J., Paik, S., Perdue, J. F., Hampton, B., Schwartz, A., Lippman, M. E. & Rosen, N. (1988). Insulin-like growth factor II mRNA expression in human breast cancer. Cancer Res, 48, 6691–6696.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia

    J P Parisot, X F Hu & J R Zalcberg

  2. Endocrine and Metabolic Unit, Austin and Repatriation Medical Centre, Melbourne, Australia

    M DeLuise

Authors
  1. J P Parisot
    View author publications

    Search author on:PubMed Google Scholar

  2. X F Hu
    View author publications

    Search author on:PubMed Google Scholar

  3. M DeLuise
    View author publications

    Search author on:PubMed Google Scholar

  4. J R Zalcberg
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Parisot, J., Hu, X., DeLuise, M. et al. Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line. Br J Cancer 79, 693–700 (1999). https://doi.org/10.1038/sj.bjc.6690112

Download citation

  • Received: 08 December 1997

  • Revised: 04 August 1998

  • Accepted: 05 August 1998

  • Published: 29 January 1999

  • Issue date: 01 February 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690112

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • breast cancer
  • IGF-1R
  • oestrogen
  • tamoxifen resistance

This article is cited by

  • Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action

    • Mitra Behroozaghdam
    • Maryam Dehghani
    • Anupam Bishayee

    Cellular and Molecular Life Sciences (2022)

  • Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer

    • Runyi Ye
    • NiJiati AiErken
    • Shenming Wang

    Oncogenesis (2021)

  • Non-coding single nucleotide variants affecting estrogen receptor binding and activity

    • Amir Bahreini
    • Kevin Levine
    • Adrian V. Lee

    Genome Medicine (2016)

  • Association of diabetes and diabetes treatment with incidence of breast cancer

    • Esther García-Esquinas
    • Elisabeth Guinó
    • Marina Pollán

    Acta Diabetologica (2016)

  • IGFBP-2 and −5: important regulators of normal and neoplastic mammary gland physiology

    • James Beattie
    • Yousef Hawsawi
    • Reem El-Gendy

    Journal of Cell Communication and Signaling (2015)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited