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Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis
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  • Published: 07 May 1999

Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis

  • L Damstrup1,2,
  • S K Kuwada3,4,
  • P J Dempsey1,
  • C L Brown1,
  • C J Hawkey1,
  • H S Poulsen2,
  • H S Wiley3 &
  • …
  • R J Coffey Jr1 

British Journal of Cancer volume 80, pages 1012–1019 (1999)Cite this article

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Summary

Colonic enterocytes, like many epithelial cells in vivo, are polarized with functionally distinct apical and basolateral membrane domains. The aims of this study were to characterize the endogenous epidermal growth factor (EGF)-like ligands expressed in two polarizing colon cancer cell lines, HCA-7 Colony 29 (HCA-7) and Caco-2, and to examine the effects of cell polarity on EGF receptor-mediated mitogenesis. HCA-7 and Caco-2 cells were grown on plastic, or as a polarized monolayer on Transwell filters. Cell proliferation was measured by 3H-thymidine incorporation and EGF receptor (EGFR) binding was assessed by Scatchard analysis. EGFR ligand expression was determined by Northern blot analysis, reverse transcription polymerase chain reaction, metabolic labelling and confocal microscopy. We found that amphiregulin (AR) was the most abundant EGFR ligand expressed in HCA-7 and Caco-2 cells. AR was localized to the basolateral surface and detected in basolateral-conditioned medium. Basolateral administration of neutralizing AR antibodies significantly reduced basal DNA replication. A single class of high-affinity EGFRs was detected in the basolateral compartment, whereas the apical compartment of polarized cells, and cells cultured on plastic, displayed two classes of receptor affinity. Basolateral administration of transforming growth factor alpha (TGF-α) or an EGFR neutralizing antibody also resulted in a dose-dependent stimulation or attenuation, respectively, of DNA replication. However, no mitogenic response was observed when these agents were added to the apical compartment or to confluent cells cultured on plastic. We conclude that amphiregulin acts as an autocrine growth factor in HCA-7 and Caco-2 cells, and EGFR ligand-induced proliferation is influenced by cellular polarity.

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  • 16 November 2011

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

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Authors and Affiliations

  1. Departments of Medicine and Cell Biology, Vanderbilt University School of Medicine and Veterans Affairs Medical Center, Nashville, 37232, TN, USA

    L Damstrup, P J Dempsey, C L Brown, C J Hawkey & R J Coffey Jr

  2. Section for Radiation Biology, University Hospital Copenhagen, Finsen Center 3993, Copenhagen, DK-2100, Denmark

    L Damstrup & H S Poulsen

  3. Departments of Medicine and Pathology, University of Utah, Salt Lake City, 84132, UT, USA

    S K Kuwada & H S Wiley

  4. Departments of Veterans Affairs Medical Center, University of Utah, Salt Lake City, 84132, UT, USA

    S K Kuwada

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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/

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Damstrup, L., Kuwada, S., Dempsey, P. et al. Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis. Br J Cancer 80, 1012–1019 (1999). https://doi.org/10.1038/sj.bjc.6690456

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  • Received: 03 September 1998

  • Accepted: 15 December 1998

  • Published: 07 May 1999

  • Issue date: 01 June 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690456

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Keywords

  • EGFR
  • polarized cells
  • colon cancer cell lines
  • ligand and proliferation

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