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  • Original Paper
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Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells

Oncogene volume 21, pages 78–86 (2002)Cite this article

Abstract

The aim of this study was to determine whether constitutive ErbB2 activation controls growth and apoptosis in colon cancer cells. Growth arrested GEO cells showed constitutive activation of ErbB2 in the absence of exogenous growth factors or serum supplementation. Higher levels of heregulin and ErbB2 activation were observed in the growth-arrested state and cell cycle re-entry was independent of exogenous growth factors. Blockade of ErbB2 activation by heregulin neutralizing antibodies and by AG879 resulted in prevention of cell cycle re-entry. This indicated that autocrine heregulin activity was responsible for growth factor independence and for cell cycle re-entry. Activation of ErbB2 was the result of heregulin mediated interaction with ErbB3 and generated downstream activation of the ERK and the PI3K/AKT pathways. Heregulin neutralizing antibody treatment of growth arrested GEO cells also generated apoptosis as reflected by PARP cleavage and DNA fragmentation indicating a cell survival signal was also induced by the constitutively activated ErbB2. The activation of AKT but not the MAPK pathway was responsible for cell survival in these cells.

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Acknowledgements

This work was supported by NIH grants CA 34432, CA 54807 (MG Brattain), CA 68316 (JKV Willson) and CA84337-01A1 (DM Dawson).

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  1. Michael G Brattain

    Present address: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, 14263, NY, USA

Authors and Affiliations

  1. Department of Surgery, University of Texas Health Science Center at San Antonio, Texas, 78284, TX, USA

    Srinivas Venkateswarlu, Patricia St Clair, Anjana Gupta & Michael G Brattain

  2. Department of Medicine, Case Western Reserve University/Ireland Cancer Center, Cleveland, 44106, Ohio, OH, USA

    Dawn M Dawson & James KV Willson

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  1. Srinivas Venkateswarlu
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  2. Dawn M Dawson
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Correspondence to Michael G Brattain.

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Venkateswarlu, S., Dawson, D., Clair, P. et al. Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. Oncogene 21, 78–86 (2002). https://doi.org/10.1038/sj.onc.1205011

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